dbSNP rs9276438: HLA-DQA2:c.*178G>A (chr6-32746739-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020056.5(HLA-DQA2):c.*178G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 543,766 control chromosomes in the GnomAD database, including 2,737 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 0.12 ( 1536 hom., cov: 32)

Exomes 𝑓: 0.060 ( 1201 hom. )

Consequence

HLA-DQA2
NM_020056.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5 link	c.*178G>A		3_prime_UTR_variant	Exon 5 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.*178G>A		3_prime_UTR_variant	Exon 5 of 5	6	NM_020056.5	ENSP00000364076.3		P01906

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17562

AN:

151736

Hom.:

1535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0773

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00520

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0672

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.0604

AC:

23674

AN:

391912

Hom.:

1201

Cov.:

AF XY:

0.0559

AC XY:

12106

AN XY:

216578

show subpopulations

African (AFR)

AF:

0.246

AC:

2871

AN:

11690

American (AMR)

AF:

0.0923

AC:

2573

AN:

27888

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

1075

AN:

14250

East Asian (EAS)

AF:

0.00106

AC:

AN:

17932

South Asian (SAS)

AF:

0.0205

AC:

1206

AN:

58754

European-Finnish (FIN)

AF:

0.00863

AC:

156

AN:

18080

Middle Eastern (MID)

AF:

0.0578

AC:

188

AN:

3250

European-Non Finnish (NFE)

AF:

0.0641

AC:

14048

AN:

219262

Other (OTH)

AF:

0.0739

AC:

1538

AN:

20806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1086

2172

3259

4345

5431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.116

AC:

17568

AN:

151854

Hom.:

1536

Cov.:

AF XY:

0.111

AC XY:

8244

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.249

AC:

10269

AN:

41288

American (AMR)

AF:

0.128

AC:

1954

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0773

AC:

268

AN:

3466

East Asian (EAS)

AF:

0.00541

AC:

AN:

5178

South Asian (SAS)

AF:

0.0146

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00520

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0672

AC:

4566

AN:

67980

Other (OTH)

AF:

0.145

AC:

306

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

719

1438

2156

2875

3594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0991

Hom.:

388

Bravo

AF:

0.137

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.45

(source)

DANN

Benign

0.45

PhyloP100

-1.2

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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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