6-32641328-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002122.5(HLA-DQA1):c.101G>A(p.Cys34Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.26 ( 4413 hom., cov: 16)
Exomes 𝑓: 0.29 ( 93358 hom. )
Failed GnomAD Quality Control
Consequence
HLA-DQA1
NM_002122.5 missense
NM_002122.5 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 0.525
Publications
57 publications found
Genes affected
HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=2.0995187E-5).
BP6
Variant 6-32641328-G-A is Benign according to our data. Variant chr6-32641328-G-A is described in ClinVar as [Benign]. Clinvar id is 1258533.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 4413 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HLA-DQA1 | NM_002122.5 | c.101G>A | p.Cys34Tyr | missense_variant | Exon 2 of 5 | ENST00000343139.11 | NP_002113.2 | |
HLA-DQA1 | XM_006715079.5 | c.101G>A | p.Cys34Tyr | missense_variant | Exon 2 of 4 | XP_006715142.1 | ||
HLA-DQA1-AS1 | XR_007059544.1 | n.-18C>T | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.256 AC: 20344AN: 79544Hom.: 4407 Cov.: 16 show subpopulations
GnomAD3 genomes
AF:
AC:
20344
AN:
79544
Hom.:
Cov.:
16
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.495 AC: 94628AN: 191328 AF XY: 0.496 show subpopulations
GnomAD2 exomes
AF:
AC:
94628
AN:
191328
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.292 AC: 266227AN: 910226Hom.: 93358 Cov.: 27 AF XY: 0.303 AC XY: 139266AN XY: 460174 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
266227
AN:
910226
Hom.:
Cov.:
27
AF XY:
AC XY:
139266
AN XY:
460174
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
4916
AN:
22306
American (AMR)
AF:
AC:
15611
AN:
28434
Ashkenazi Jewish (ASJ)
AF:
AC:
5767
AN:
15938
East Asian (EAS)
AF:
AC:
3622
AN:
25830
South Asian (SAS)
AF:
AC:
24122
AN:
62516
European-Finnish (FIN)
AF:
AC:
8038
AN:
37950
Middle Eastern (MID)
AF:
AC:
1535
AN:
3648
European-Non Finnish (NFE)
AF:
AC:
192998
AN:
676488
Other (OTH)
AF:
AC:
9618
AN:
37116
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.293
Heterozygous variant carriers
0
6258
12516
18775
25033
31291
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.256 AC: 20360AN: 79622Hom.: 4413 Cov.: 16 AF XY: 0.251 AC XY: 9728AN XY: 38744 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
20360
AN:
79622
Hom.:
Cov.:
16
AF XY:
AC XY:
9728
AN XY:
38744
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
4841
AN:
22648
American (AMR)
AF:
AC:
1407
AN:
6150
Ashkenazi Jewish (ASJ)
AF:
AC:
558
AN:
1740
East Asian (EAS)
AF:
AC:
430
AN:
2302
South Asian (SAS)
AF:
AC:
607
AN:
2668
European-Finnish (FIN)
AF:
AC:
749
AN:
5478
Middle Eastern (MID)
AF:
AC:
45
AN:
114
European-Non Finnish (NFE)
AF:
AC:
11243
AN:
36898
Other (OTH)
AF:
AC:
271
AN:
1076
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.300
Heterozygous variant carriers
0
838
1676
2515
3353
4191
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
1866
ESP6500EA
AF:
AC:
3996
ExAC
AF:
AC:
67297
Asia WGS
AF:
AC:
1584
AN:
3374
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Jul 15, 2020
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is associated with the following publications: (PMID: 25349203) -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Vest4
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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