Genetic Variant HLA-DQA2:c.613+18C>T (chr6-32746090-C-T) – 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.613+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,603,848 control chromosomes in the GnomAD database, including 18,921 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 ( 778 hom., cov: 35)

Exomes 𝑓: 0.17 ( 18143 hom. )

Consequence

HLA-DQA2
NM_020056.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

31 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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5 link	c.613+18C>T		intron_variant	Intron 3 of 4	ENST00000374940.4	NP_064440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA2	ENST00000374940.4 link	c.613+18C>T		intron_variant	Intron 3 of 4	6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18844

AN:

151530

Hom.:

777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.0247

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.120

GnomAD2 exomes

AF:

0.133

AC:

32790

AN:

245916

AF XY:

0.137

show subpopulations

Gnomad AFR exome

AF:

0.0536

Gnomad AMR exome

AF:

0.0639

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.0211

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.169

AC:

245381

AN:

1452198

Hom.:

18143

Cov.:

AF XY:

0.168

AC XY:

121184

AN XY:

722554

show subpopulations

African (AFR)

AF:

0.0518

AC:

1731

AN:

33424

American (AMR)

AF:

0.0666

AC:

2970

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3543

AN:

26042

East Asian (EAS)

AF:

0.0158

AC:

625

AN:

39626

South Asian (SAS)

AF:

0.120

AC:

10326

AN:

86056

European-Finnish (FIN)

AF:

0.186

AC:

9715

AN:

52248

Middle Eastern (MID)

AF:

0.124

AC:

710

AN:

5742

European-Non Finnish (NFE)

AF:

0.187

AC:

206146

AN:

1104334

Other (OTH)

AF:

0.160

AC:

9615

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

12866

25732

38597

51463

64329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7302

14604

21906

29208

36510

<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:

0.124

AC:

18837

AN:

151650

Hom.:

778

Cov.:

AF XY:

0.123

AC XY:

9108

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.0560

AC:

2326

AN:

41514

American (AMR)

AF:

0.108

AC:

1644

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

462

AN:

3464

East Asian (EAS)

AF:

0.0247

AC:

128

AN:

5176

South Asian (SAS)

AF:

0.0938

AC:

451

AN:

4808

European-Finnish (FIN)

AF:

0.176

AC:

1858

AN:

10530

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11607

AN:

67588

Other (OTH)

AF:

0.119

AC:

249

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

739

1478

2217

2956

3695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.154

Hom.:

3722

Asia WGS

AF:

0.0700

AC:

247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.9

(source)

DANN

Benign

0.84

PhyloP100

-1.4

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