dbSNP rs3208181: HLA-DQA2:p.Tyr59Tyr (chr6-32745253-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020056.5(HLA-DQA2):c.177T>C(p.Tyr59Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,595,902 control chromosomes in the GnomAD database, including 252,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 22996 hom., cov: 30)

Exomes 𝑓: 0.57 ( 229810 hom. )

Consequence

HLA-DQA2
NM_020056.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

17 publications found

Variant links:

Genes affected

HLA-DQA2 (HGNC:4943): (major histocompatibility complex, class II, DQ alpha 2) This gene belongs to the HLA class II alpha chain family. The encoded protein forms a heterodimer with a class II beta chain. It is located in intracellular vesicles and plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (B lymphocytes, dendritic cells, macrophages) and are used to present antigenic peptides on the cell surface to be recognized by CD4 T-cells. [provided by RefSeq, Jun 2010]

HLA-DQA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5 link	c.177T>C	p.Tyr59Tyr	synonymous_variant	Exon 2 of 5	ENST00000374940.4	NP_064440.1	P01906Q76NI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA2	ENST00000374940.4 link	c.177T>C	p.Tyr59Tyr	synonymous_variant	Exon 2 of 5	6	NM_020056.5	ENSP00000364076.3		P01906

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

84939

AN:

147010

Hom.:

22967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.605

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.641

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.633

GnomAD2 exomes

AF:

0.626

AC:

156313

AN:

249618

AF XY:

0.626

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.725

Gnomad ASJ exome

AF:

0.637

Gnomad EAS exome

AF:

0.830

Gnomad FIN exome

AF:

0.572

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.623

GnomAD4 exome

AF:

0.565

AC:

819089

AN:

1448778

Hom.:

229810

Cov.:

AF XY:

0.568

AC XY:

409621

AN XY:

720728

show subpopulations

African (AFR)

AF:

0.632

AC:

20988

AN:

33226

American (AMR)

AF:

0.694

AC:

30589

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.632

AC:

16372

AN:

25908

East Asian (EAS)

AF:

0.749

AC:

29560

AN:

39484

South Asian (SAS)

AF:

0.654

AC:

55744

AN:

85224

European-Finnish (FIN)

AF:

0.559

AC:

29689

AN:

53066

Middle Eastern (MID)

AF:

0.651

AC:

3733

AN:

5738

European-Non Finnish (NFE)

AF:

0.542

AC:

597861

AN:

1102168

Other (OTH)

AF:

0.577

AC:

34553

AN:

59888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17550

35101

52651

70202

87752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.578

AC:

85025

AN:

147124

Hom.:

22996

Cov.:

AF XY:

0.583

AC XY:

41900

AN XY:

71854

show subpopulations

African (AFR)

AF:

0.614

AC:

24664

AN:

40152

American (AMR)

AF:

0.639

AC:

9340

AN:

14610

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

2040

AN:

3370

East Asian (EAS)

AF:

0.742

AC:

3603

AN:

4858

South Asian (SAS)

AF:

0.640

AC:

2913

AN:

4552

European-Finnish (FIN)

AF:

0.556

AC:

5735

AN:

10318

Middle Eastern (MID)

AF:

0.655

AC:

190

AN:

290

European-Non Finnish (NFE)

AF:

0.525

AC:

34688

AN:

66074

Other (OTH)

AF:

0.638

AC:

1301

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

1633

3265

4898

6530

8163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.573

Hom.:

10466

Asia WGS

AF:

0.667

AC:

2317

AN:

3478

EpiCase

AF:

0.600

EpiControl

AF:

0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.11

(source)

DANN

Benign

0.31

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs3208181

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over