Genetic Variant NM_020056.5:c.*563C>T (chr6-32747124-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.*563C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 157,292 control chromosomes in the GnomAD database, including 1,607 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 ( 1588 hom., cov: 27)

Exomes 𝑓: 0.046 ( 19 hom. )

Consequence

HLA-DQA2
NM_020056.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.599

Publications

6 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5 link	c.*563C>T		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.*563C>T		3_prime_UTR_variant	Exon 5 of 5	6	NM_020056.5	ENSP00000364076.3		P01906

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17080

AN:

149116

Hom.:

1586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0774

Gnomad EAS

AF:

0.00566

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00505

Gnomad MID

AF:

0.0353

Gnomad NFE

AF:

0.0670

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.0463

AC:

374

AN:

8076

Hom.:

Cov.:

AF XY:

0.0430

AC XY:

187

AN XY:

4352

show subpopulations

African (AFR)

AF:

0.135

AC:

AN:

American (AMR)

AF:

0.0801

AC:

133

AN:

1660

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

426

South Asian (SAS)

AF:

0.0130

AC:

AN:

846

European-Finnish (FIN)

AF:

0.00862

AC:

AN:

116

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0419

AC:

191

AN:

4558

Other (OTH)

AF:

0.0786

AC:

AN:

318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.115

AC:

17088

AN:

149216

Hom.:

1588

Cov.:

AF XY:

0.110

AC XY:

8016

AN XY:

72696

show subpopulations

African (AFR)

AF:

0.248

AC:

9878

AN:

39884

American (AMR)

AF:

0.128

AC:

1912

AN:

14920

Ashkenazi Jewish (ASJ)

AF:

0.0774

AC:

267

AN:

3450

East Asian (EAS)

AF:

0.00548

AC:

AN:

5110

South Asian (SAS)

AF:

0.0137

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00505

AC:

AN:

10094

Middle Eastern (MID)

AF:

0.0345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0670

AC:

4539

AN:

67738

Other (OTH)

AF:

0.143

AC:

296

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

582

1163

1745

2326

2908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0908

Hom.:

336

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

-0.93

CADD

Benign

4.7

(source)

DANN

Benign

0.64

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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