Variant 6-32641426-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_002122.5(HLA-DQA1):c.199A>G(p.Thr67Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,070,518 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.000084 ( 2 hom., cov: 15)

Exomes 𝑓: 0.00016 ( 52 hom. )

Consequence

HLA-DQA1
NM_002122.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.77

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40534523).

BP6

Variant 6-32641426-A-G is Benign according to our data. Variant chr6-32641426-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3257709.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5 link	c.199A>G	p.Thr67Ala	missense_variant	Exon 2 of 5	ENST00000343139.11	NP_002113.2	P01909A0A173ADG5Q8MH44
HLA-DQA1	XM_006715079.5 link	c.199A>G	p.Thr67Ala	missense_variant	Exon 2 of 4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11 link	c.199A>G	p.Thr67Ala	missense_variant	Exon 2 of 5	6	NM_002122.5	ENSP00000339398.5		P01909

Frequencies

GnomAD3 genomes

AF:

0.0000844

AC:

AN:

94764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000368

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000122

AC:

AN:

196278

Hom.:

AF XY:

0.000168

AC XY:

AN XY:

107314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000183

Gnomad OTH exome

AF:

0.000642

GnomAD4 exome

AF:

0.000161

AC:

157

AN:

975754

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

491690

show subpopulations

Gnomad4 AFR exome

AF:

0.0000790

Gnomad4 AMR exome

AF:

0.0000878

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000103

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.0000844

AC:

AN:

94764

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

46082

show subpopulations

Gnomad4 AFR

AF:

0.0000368

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000163

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000106

Hom.:

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HLA-DQA1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

.;.;T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.73

.;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Vest4

0.69

MVP

0.47

MPC

1.9

ClinPred

0.36

GERP RS

3.8

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over