Genetic Variant HLA-DQA2:c.331+83A>G (chr6-32745490-A-G) – 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.331+83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,435,500 control chromosomes in the GnomAD database, including 11,845 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 0.11 ( 1177 hom., cov: 30)

Exomes 𝑓: 0.11 ( 10668 hom. )

Consequence

HLA-DQA2
NM_020056.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

Publications

28 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5 link	c.331+83A>G		intron_variant	Intron 2 of 4	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.331+83A>G		intron_variant	Intron 2 of 4	6	NM_020056.5	ENSP00000364076.3		P01906

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16808

AN:

150278

Hom.:

1180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0681

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0902

Gnomad MID

AF:

0.109

Gnomad NFE

AF:

0.0922

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.108

AC:

138304

AN:

1285102

Hom.:

10668

AF XY:

0.109

AC XY:

70080

AN XY:

644288

show subpopulations

African (AFR)

AF:

0.0703

AC:

2083

AN:

29642

American (AMR)

AF:

0.342

AC:

14191

AN:

41516

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

2633

AN:

23198

East Asian (EAS)

AF:

0.322

AC:

12436

AN:

38674

South Asian (SAS)

AF:

0.170

AC:

13165

AN:

77480

European-Finnish (FIN)

AF:

0.0954

AC:

4728

AN:

49542

Middle Eastern (MID)

AF:

0.117

AC:

629

AN:

5368

European-Non Finnish (NFE)

AF:

0.0850

AC:

82019

AN:

965254

Other (OTH)

AF:

0.118

AC:

6420

AN:

54428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6261

12523

18784

25046

31307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3078

6156

9234

12312

15390

<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:

0.112

AC:

16815

AN:

150398

Hom.:

1177

Cov.:

AF XY:

0.116

AC XY:

8482

AN XY:

73434

show subpopulations

African (AFR)

AF:

0.0680

AC:

2785

AN:

40936

American (AMR)

AF:

0.222

AC:

3352

AN:

15068

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

397

AN:

3456

East Asian (EAS)

AF:

0.347

AC:

1742

AN:

5024

South Asian (SAS)

AF:

0.184

AC:

873

AN:

4752

European-Finnish (FIN)

AF:

0.0902

AC:

931

AN:

10322

Middle Eastern (MID)

AF:

0.113

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0922

AC:

6226

AN:

67554

Other (OTH)

AF:

0.115

AC:

241

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

696

1392

2087

2783

3479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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:

0.108

Hom.:

4887

Asia WGS

AF:

0.253

AC:

878

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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