Variant chr6-32641328-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 12/17 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

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.525

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:

HLA-DQA1-AS1 (HGNC:):

HLA-DQA1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HLA-DQA1	NM_002122.5 linkuse as main transcript	c.101G>A	p.Cys34Tyr	missense_variant	2/5	ENST00000343139.11
HLA-DQA1	XM_006715079.5 linkuse as main transcript	c.101G>A	p.Cys34Tyr	missense_variant	2/4
HLA-DQA1-AS1	XR_007059544.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000343139.11 linkuse as main transcript	c.101G>A	p.Cys34Tyr	missense_variant	2/5		NM_002122.5	P1

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

20344

AN:

79544

Hom.:

4407

Cov.:

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

GnomAD3 exomes

AF:

0.495

AC:

94628

AN:

191328

Hom.:

36252

AF XY:

0.496

AC XY:

51363

AN XY:

103594

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 SAS exome

AF:

0.434

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.:

AF XY:

0.303

AC XY:

139266

AN XY:

460174

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.549

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.256

AC:

20360

AN:

79622

Hom.:

4413

Cov.:

AF XY:

0.251

AC XY:

9728

AN XY:

38744

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.589

Hom.:

32572

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

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

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.075

DANN

Benign

0.23

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0020

MetaRNN

Benign

0.000021

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.39

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

GERP RS

-0.28

gMVP

0.60

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

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