RHD*04.01 - RHD*DIVa<br /><small>(ISBT table: RHD partial D v5.0)</small><br />

Molecular Data Phenotype Haplotype Alloimmunization Reports 2D diagram Structure Links References

RHD04.01 - RHDDIVa
(ISBT table: RHD partial D v5.0)

This entry is an RHD allele.

DIV Type 1.1 (obsolete), DIV type 1, DIV type 1.0, DIV.I, DIVa, DIVa (Bel.) (obsolete), DIVa Type 1, DIVa-2 (obsolete), RHD(L62F,A137V,N152T,D350H), RHD*186G>T,410C>T,455A>C,1048G>C, RHD*186T,410T,455C,1048C, RHD*186T,410T,455C,1048C (DIVa),

Download VCF file

Molecular data

Nucleotides: 186G>T; 410C>T; 455A>C; 1048G>C;

Amino acids: L62F; A137V; N152T; D350H;

Hybrid allele encompassing at least one RHCE exon: no

Comments on the molecular basis:

initially described without c.410C>T p.A137V
c.410C>T A137V corrected by family study
410C>T corrected by family study
see also "Additional comments" section on the RhesusBase http://www.rhesusbase.info/RHDDIVa-2.htm
"original DIVa report missed 410C>T change"

Extracellular position of one or more amino acid substitutions:

residue 350 is predicted to be extracellular

Splicing:

Unconventional prediction methods:

Phenotype

Main D phenotype: variable/discrepant (last update: May 4, 2020)

Reports by D phenotype

Other RH phenotypes: RH:-2, -3, -8, -23, 30, -32, -50, -56,

RH:-2 inferred from the reported RHCE phenotypes of the carriers
RH:-3 inferred from the reported RHCE phenotypes of the carriers
RH:-8 Table 2
RH:-23 sample DIVa (Bel.)
RH:30 review sample DIVa (Bel.) Table 2
RH:-32
RH:-50 sample DIVa (Bel.)
RH:-56

Serology with monoclonal anti-D

more than 5 anti-D non-reactive with variant, out of approx 20 monoclonal IgG tested (Table 3)
epitope pattern (Table 1)

Antigen Density (Ag/RBC)

9300 Ag/RBC (Table 2)
20005 Ag/RBC, with 6 monoclonal IgG anti-D

More phenotype data

Rhesus Similarity Index

Haplotype

Main CcEe phenotype association: ce (last update: June 20, 2020)

Number of samples reported by haplotype
	ce	Ce	cE
ce	1	1	0
Ce		0	0
cE			0
CE

Reports by CcEe phenotype

with ce

with Ce

with Ccee

Main allele association: RHCE*01.02.01 (RHCE*ceTI)

Reports by allele association

RHCE*ceTI
- 1 sample
- 5 samples
- 1 sample
- 4 samples
- 1 sample
RHCE*ceTI partly characterized
- 3 samples
RHCE*ceTI(D2)
- 5 samples
RHCE*01 or RHCE*ce48,733,1006
- 1 sample
RHCE*ceMO or RHCE*ce-D(5)-ce
- 1 sample
RHCE*ceVS.01 or RHCE*ceTI
- 1 sample
RHCE*ce.01(105T) or RHCE*ceTI
- 1 sample
RHCE*ceVS.03 or RHCE*ce.01−DIVa(2−3,5−9)
- 1 sample
RHCE*ceAG or RHCE*ceTI
- 1 sample
RHCE*ceEK or RHCE*ceTI
- 1 sample
RHCE*01
- 1 sample

Alloimmunization

Antibodies in carriers

Antibody specificity: D (RH1)

Summary: probably allo-anti-D (last update: May 16, 2020)

Detailed information

et al

Ab specificity: D (RH1)
Number (auto- or allo-):
Number listed as allo-: 1
Number listed as auto-:
Number of carriers of the allele assessed:
DAT: negative
Autologuous control: ND
Elution: ND
Autoadsorption: ND
Titer: 256
Was anti-LW excluded?: yes
Other antibodies detected: ND
Cross matches (with Ab and RBCs from different partial types): ND
Transfusion history: none
Pregnancy history:
Anti-D Ig history: ND, probably none
Context: ND
Hemolytic consequences: ND
Comment:

et al

Ab specificity: D (RH1)
Number (auto- or allo-):
Number listed as allo-: 1
Number listed as auto-:
Number of carriers of the allele assessed:
DAT: positive
Autologuous control: ND
Elution: negative
Autoadsorption: ND
Titer: 16
Was anti-LW excluded?: yes
Other antibodies detected: ND
Cross matches (with Ab and RBCs from different partial types): ND
Transfusion history: none
Pregnancy history:
Anti-D Ig history: ND, probably none
Context: ND
Hemolytic consequences: ND
Comment:

et al

Ab specificity: D (RH1)
Number (auto- or allo-): 1
Number listed as allo-:
Number listed as auto-:
Number of carriers of the allele assessed:
DAT: ND
Autologuous control: ND
Elution: ND
Autoadsorption: ND
Titer: ND
Was anti-LW excluded?: ND
Other antibodies detected: ND
Cross matches (with Ab and RBCs from different partial types): ND
Transfusion history: ND, probable
Pregnancy history:
Anti-D Ig history: ND
Context: among 17 SCD patients with anti-D
Hemolytic consequences:
Comment:

et al

Ab specificity: D (RH1)
Number (auto- or allo-): 1
Number listed as allo-:
Number listed as auto-:
Number of carriers of the allele assessed:
DAT:
Autologuous control:
Elution:
Autoadsorption:
Titer:
Was anti-LW excluded?:
Other antibodies detected:
Cross matches (with Ab and RBCs from different partial types):
Transfusion history:
Pregnancy history:
Anti-D Ig history:
Context:
Hemolytic consequences:
Comment:

et al

Ab specificity: D (RH1)
Number (auto- or allo-):
Number listed as allo-: 2
Number listed as auto-:
Number of carriers of the allele assessed:
DAT: ND
Autologuous control: ND
Elution: ND
Autoadsorption: ND
Titer: ND
Was anti-LW excluded?: ND
Other antibodies detected: ND
Cross matches (with Ab and RBCs from different partial types): ND
Transfusion history: yes, number and phenotypes ND
Pregnancy history:
Anti-D Ig history: ND, probably none
Context: among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols
Hemolytic consequences: none of the 13 patients with delayed hemolytic transfusion reactions or decreased survival of transfused RBCs had this allele
Comment: study does not detail serology for each sample, but mentions performing DAT, autologuous control, eluate studies and adsorption on autologuous RBCs to aid the differenciation of autoantibodies and alloantibodies

et al

Ab specificity: D (RH1)
Number (auto- or allo-): 6
Number listed as allo-:
Number listed as auto-:
Number of carriers of the allele assessed: ND
DAT: ND
Autologuous control: ND
Elution: ND
Autoadsorption: ND
Titer: ND
Was anti-LW excluded?: ND
Other antibodies detected: ND
Cross matches (with Ab and RBCs from different partial types): ND
Transfusion history: ND
Pregnancy history:
Anti-D Ig history: ND
Context: ND
Hemolytic consequences: none
Comment:

et al

Ab specificity: D (RH1)
Number (auto- or allo-): 1 (heterozygous with RHef00452)
Number listed as allo-:
Number listed as auto-:
Number of carriers of the allele assessed:
DAT: ND
Autologuous control: ND
Elution: ND
Autoadsorption: ND
Titer: ND
Was anti-LW excluded?: ND
Other antibodies detected: none
Cross matches (with Ab and RBCs from different partial types): ND
Transfusion history: 181 RBC exposures
Pregnancy history:
Anti-D Ig history: ND, probably none
Context: SCD child
Hemolytic consequences: none
Comment: Anti-D not detectable after 1 month

et al

Ab specificity: D (RH1)
Number (auto- or allo-):
Number listed as allo-: no new case detailed (listed as allo-anti-D)
Number listed as auto-: NA
Number of carriers of the allele assessed: NA
DAT: NA
Autologuous control: NA
Elution: NA
Autoadsorption: NA
Titer: NA
Was anti-LW excluded?: NA
Other antibodies detected: NA
Cross matches (with Ab and RBCs from different partial types): NA
Transfusion history: NA
Pregnancy history:
Anti-D Ig history: NA
Context: NA
Hemolytic consequences: NA
Comment: list of D variants associated with alloanti-D formation

Antibodies in D negative recipients

Alloimmunization in recipients: expected to be possible, see phenotype data

Reports

Summary: several descriptions, in individuals of African descent, or compatible with such descent (last update: April 28, 2020)

Detailed reports

1 sample in the French population (sample DIVa (Bel.))
6/21 21 samples referred for anti-D in a D positive individual African American or Hispanic, in the USA population (Table 3)
1/10 (heterozygous with RHef00020) individuals with D positive phenotype Bantu, subgroup Teke, Kukuya from villages around Djambala city
1/45 (prevalence among weak D phenotype) or 1/12672 (phenotypic prevalence in population) 45 patients with weak D phenotype were genotyped in a cohort of 12672 patients from a public hospital Argentinean
0/43 (prevalence among weak D phenotype) or 0/5707 (phenotypic prevalence in population) 43 patients with weak D phenotype were genotyped in a cohort of 5707 patients from a private laboratory Argentinean
1/205 weak D phenotype African descent, in the French population
3/163 selected variants included for the development of a genotyping assay mainly in the Dutch population (samples may have been included in other studies)
0/78156 donations, of which 60965 had D positive phenotype. 8 donors with RHef00606 were detected by serologic screening and further characterized by molecular analysis. None of those was RHef00067 in the German population, southwestern Germany
8 alleles in 226 patients SCD children systematically genotyped in an alloimmunization study in the USA population (Philadelphia)
1/50 (heterozygous with RHef00008) among 50 donors, the majority referred because of ambiguous RH5 antigen typing, found to have RHCE*ceMO (44 with RHef00008, 6 with RHef00442) in the USA population
6/316 (2 homo- or hemizygous, 1 heterozygous with RHef00447, 3 with RHef00442) 316 (280 D positive and 36 D negative) donors were genotyped African descent (FY:-1,-2) in the French population
0/127 the cohort was composed of 77 Tswa from Congo, 36 Biaka from Central African Republic, 14 Mbuti from Democratic Republic of the Congo Pygmoid Central African
4/220 the cohort was composed of 164 Teke-Congolese (ethnic groups: 60 Akwa, 52 Mbochi, 52 Kuyu) from Congo, 19 Mandenka from Senegal, 25 Yoruba from Nigeria, 12 Bantu from Kenya Nonpygmoid Central African
1/360 donors with atypical D phenotype (discrepancies or reactivity weaker than 3+) Brazilian
5/48 (samples heterozygous with RHef00452) among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols African Brazilian
1/400 among random blood and bone marrow donors genotyped for RHD In the Brazilian population, Parana state, Southern Brazil
1 sample with a D positive phenotype and anti-D Black, in the USA population
16/94 donors with discreapancies in D typing Southeast Brazil
3 hemizygotes, 3 heterozygotes among 278 samples selected for the development of nonspecific quantitative next-generation sequencing. (non-random samples, may have been reported in other studies)

Allele or phenotype frequency

highest estimate 1/26087 estimated phenotype frequency among 78156 blood donations of which 60965 had D positive phenotype in the German population, southwestern Germany
0.014 allele frequency among 140 SCD patients African American (in the USA population)
0.013 allele frequency among 480 African American donors African American, in the USA population
0,029 allele frequency from molecular typing of 101 random samples Dogon Malian

2D diagram

Structure mapping

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Links

The Human RhesusBase
Genbank: HF549086 LN680105
Erythrogene

References

International Society of Blood Transfusion et al. International Society of Blood Transfusion (ISBT) allele table Online ressource, 1935. — Online ressource — [RHeference]
Rouillac C et al. Transcript analysis of D category phenotypes predicts hybrid Rh D-CE-D proteins associated with alteration of D epitopes. Blood, 1995. [Citation] [RHeference]
Avent ND et al. Molecular basis of the D variant phenotypes DNU and DII allows localization of critical amino acids required for expression of Rh D epitopes epD3, 4 and 9 to the sixth external domain of the Rh D protein. Br J Haematol, 1997. [Citation] [RHeference]
Avent ND et al. The rhesus blood group system: insights from recent advances in molecular biology. Transfus Med Rev, 1999. [Citation] [RHeference]
Liu W et al. Site-directed mutagenesis of the human D antigen: definition of D epitopes on the sixth external domain of the D protein expressed on K562 cells. Transfusion, 1999. [Citation] [RHeference]
Noizat-Pirenne F et al. Rare RHCE phenotypes in black individuals of Afro-Caribbean origin: identification and transfusion safety. Blood, 2002. [Citation] [RHeference]
Wagner FF et al. The DAU allele cluster of the RHD gene. Blood, 2002. [Citation] [RHeference]
Westhoff CM et al. A new hybrid RHCE gene (CeNR) is responsible for expression of a novel antigen. Transfusion, 2004. [Citation] [RHeference]
Chen Q et al. Random survey for RHD alleles among D+ European persons. Transfusion, 2005. [Citation] [RHeference]
Grootkerk-Tax MG et al. RHD(T201R, F223V) cluster analysis in five different ethnic groups and serologic characterization of a new Ethiopian variant DARE, the DIII type 6, and the RHD(F223V). Transfusion, 2006. [Citation] [RHeference]
Westhoff CM et al. Rh complexities: serology and DNA genotyping. Transfusion, 2007. [Citation] [RHeference]
Flegel WA et al. D variants at the RhD vestibule in the weak D type 4 and Eurasian D clusters. Transfusion, 2009. [Citation] [RHeference]
Touinssi M et al. Molecular analysis of inactive and active RHD alleles in native Congolese cohorts. Transfusion, 2009. [Citation] [RHeference]
Wagner FF and Flegel WA et al. The Human RhesusBase Online ressource, 2011. — Online ressource — [RHeference]
Noizat-Pirenne F et al. Relevance of RH variants in transfusion of sickle cell patients. Transfus Clin Biol, 2011. [Citation] [RHeference]
Brajovich ME et al. Comprehensive analysis of RHD alleles in Argentineans with variant D phenotypes. Transfusion, 2012. [Citation] [RHeference]
M E Reid et al. DIVa and DIVa-2 are Encoded by the Same RHD Allele Transfusion, 2012. — Abstract — [RHeference]
Westhoff CM et al. RHCE*ceTI encodes partial c and partial e and is often in cis to RHD*DIVa. Transfusion, 2013. [Citation] [RHeference]
Chou ST et al. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood, 2013. [Citation] [RHeference]
von Zabern I et al. D category IV: a group of clinically relevant and phylogenetically diverse partial D. Transfusion, 2013. [Citation] [RHeference]
Granier T et al. A comprehensive survey of both RHD and RHCE allele frequencies in sub-Saharan Africa. Transfusion, 2013. [Citation] [RHeference]
Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 2013. [Citation] [RHeference]
Westhoff CM et al. RHCE*ceMO is frequently in cis to RHD*DAU0 and encodes a hr(S) -, hr(B) -, RH:-61 phenotype in black persons: clinical significance. Transfusion, 2013. [Citation] [RHeference]
Haer-Wigman L et al. RHD and RHCE variant and zygosity genotyping via multiplex ligation-dependent probe amplification. Transfusion, 2013. [Citation] [RHeference]
Arnoni CP et al. How do we identify RHD variants using a practical molecular approach? Transfusion, 2014. [Citation] [RHeference]
Wagner FF et al. The Rhesus Site. Transfus Med Hemother, 2014. [Citation] [RHeference]
Kappler-Gratias S et al. Systematic RH genotyping and variant identification in French donors of African origin. Blood Transfus, 2014. [Citation] [RHeference]
Reid ME et al. Genomic analyses of RH alleles to improve transfusion therapy in patients with sickle cell disease. Blood Cells Mol Dis, 2014. [Citation] [RHeference]
Ba A et al. RH diversity in Mali: characterization of a new haplotype RHD*DIVa/RHCE*ceTI(D2). Transfusion, 2015. [Citation] [RHeference]
A C Gaspardi et al. RHD variants in blood donors from Southeast Brazil. Transfusion, 2015. — Abstract — [RHeference]
Sippert E et al. Variant RH alleles and Rh immunisation in patients with sickle cell disease. Blood Transfus, 2015. [Citation] [RHeference]
Srivastava K et al. The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens. Transfusion, 2016. [Citation] [RHeference]
Zacarias JM et al. Frequency of RHD variants in Brazilian blood donors from Parana State, Southern Brazil. Transfus Apher Sci, 2016. [Citation] [RHeference]
Aeschlimann J et al. Four novel silenced RHCE. Transfusion, 2018. [Citation] [RHeference]
Stef M et al. RH genotyping by nonspecific quantitative next-generation sequencing. Transfusion, 2020. [Citation] [RHeference]
Floch A et al. Comment from Rheference Online ressource, 2020. — Online ressource — [RHeference]

Last update: Jan. 8, 2021

RHD*04.01 - RHD*DIVa(ISBT table: RHD partial D v5.0)

Reports by D phenotype

Other RH phenotypes: RH:-2, -3, -8, -23, 30, -32, -50, -56,

Serology with monoclonal anti-D

Antigen Density (Ag/RBC)

More phenotype data

Rhesus Similarity Index

Reports by CcEe phenotype

Reports by allele association

Antibodies in carriers

Antibody specificity: D (RH1)

Detailed information

Antibodies in D negative recipients

Detailed reports

Allele or phenotype frequency

RHD04.01 - RHDDIVa
(ISBT table: RHD partial D v5.0)