6-32641328-G-A

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

Scores

16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.525

Publications

57 publications found
Variant links:
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]
HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

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-DQA1NM_002122.5 linkc.101G>A p.Cys34Tyr missense_variant Exon 2 of 5 ENST00000343139.11 NP_002113.2 P01909A0A173ADG5Q8MH44
HLA-DQA1XM_006715079.5 linkc.101G>A p.Cys34Tyr missense_variant Exon 2 of 4 XP_006715142.1
HLA-DQA1-AS1XR_007059544.1 linkn.-18C>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLA-DQA1ENST00000343139.11 linkc.101G>A p.Cys34Tyr missense_variant Exon 2 of 5 6 NM_002122.5 ENSP00000339398.5 P01909

Frequencies

GnomAD3 genomes
AF:
0.256
AC:
20344
AN:
79544
Hom.:
4407
Cov.:
16
show subpopulations
Gnomad AFR
AF:
0.214
Gnomad AMI
AF:
0.381
Gnomad AMR
AF:
0.228
Gnomad ASJ
AF:
0.321
Gnomad EAS
AF:
0.186
Gnomad SAS
AF:
0.228
Gnomad FIN
AF:
0.137
Gnomad MID
AF:
0.383
Gnomad NFE
AF:
0.305
Gnomad OTH
AF:
0.256
GnomAD2 exomes
AF:
0.495
AC:
94628
AN:
191328
AF XY:
0.496
show subpopulations
Gnomad AFR exome
AF:
0.417
Gnomad AMR exome
AF:
0.662
Gnomad ASJ exome
AF:
0.556
Gnomad EAS exome
AF:
0.450
Gnomad FIN exome
AF:
0.403
Gnomad NFE exome
AF:
0.496
Gnomad OTH exome
AF:
0.458
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.292
AC:
266227
AN:
910226
Hom.:
93358
Cov.:
27
AF XY:
0.303
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:
0.220
AC:
4916
AN:
22306
American (AMR)
AF:
0.549
AC:
15611
AN:
28434
Ashkenazi Jewish (ASJ)
AF:
0.362
AC:
5767
AN:
15938
East Asian (EAS)
AF:
0.140
AC:
3622
AN:
25830
South Asian (SAS)
AF:
0.386
AC:
24122
AN:
62516
European-Finnish (FIN)
AF:
0.212
AC:
8038
AN:
37950
Middle Eastern (MID)
AF:
0.421
AC:
1535
AN:
3648
European-Non Finnish (NFE)
AF:
0.285
AC:
192998
AN:
676488
Other (OTH)
AF:
0.259
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

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5012
10024
15036
20048
25060
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.256
AC:
20360
AN:
79622
Hom.:
4413
Cov.:
16
AF XY:
0.251
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:
0.214
AC:
4841
AN:
22648
American (AMR)
AF:
0.229
AC:
1407
AN:
6150
Ashkenazi Jewish (ASJ)
AF:
0.321
AC:
558
AN:
1740
East Asian (EAS)
AF:
0.187
AC:
430
AN:
2302
South Asian (SAS)
AF:
0.228
AC:
607
AN:
2668
European-Finnish (FIN)
AF:
0.137
AC:
749
AN:
5478
Middle Eastern (MID)
AF:
0.395
AC:
45
AN:
114
European-Non Finnish (NFE)
AF:
0.305
AC:
11243
AN:
36898
Other (OTH)
AF:
0.252
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

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
200
400
600
800
1000
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.583
Hom.:
44721
ESP6500AA
AF:
0.424
AC:
1866
ESP6500EA
AF:
0.465
AC:
3996
ExAC
AF:
0.556
AC:
67297
Asia WGS
AF:
0.469
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
0.075
DANN
Benign
0.23
DEOGEN2
Benign
0.0012
.;.;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0020
N
LIST_S2
Benign
0.70
.;.;T;T
MetaRNN
Benign
0.000021
T;T;T;T
MetaSVM
Benign
-0.96
T
PhyloP100
0.53
PrimateAI
Benign
0.39
T
PROVEAN
Benign
4.8
N;N;N;N
REVEL
Benign
0.28
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Vest4
0.060
MPC
1.4
ClinPred
0.0047
T
GERP RS
-0.28
gMVP
0.60
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1129740; hg19: chr6-32609105; COSMIC: COSV58237735; COSMIC: COSV58237735; API