Genetic Variant HLA-DQA1:p.Lys76* (chr6-32641453-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002122.5(HLA-DQA1):c.226A>T(p.Lys76*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 13)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DQA1
NM_002122.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

Publications

12 publications found

Variant links:

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

HLA-DQA1 links:

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

HLA-DQA1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HLA-DQA1	NM_002122.5 link	c.226A>T	p.Lys76*	stop_gained	Exon 2 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5 link	c.226A>T	p.Lys76*	stop_gained	Exon 2 of 4		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1 link	n.-143T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11 link	c.226A>T	p.Lys76*	stop_gained	Exon 2 of 5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

84074

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

929176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

465856

African (AFR)

AF:

0.00

AC:

AN:

24148

American (AMR)

AF:

0.00

AC:

AN:

19494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15358

East Asian (EAS)

AF:

0.00

AC:

AN:

26226

South Asian (SAS)

AF:

0.00

AC:

AN:

63068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

699880

Other (OTH)

AF:

0.00

AC:

AN:

39088

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

84074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

40746

African (AFR)

AF:

0.00

AC:

AN:

24008

American (AMR)

AF:

0.00

AC:

AN:

6732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1788

East Asian (EAS)

AF:

0.00

AC:

AN:

2668

South Asian (SAS)

AF:

0.00

AC:

AN:

2664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

38272

Other (OTH)

AF:

0.00

AC:

AN:

1026

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Benign

0.73

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

PhyloP100

-2.3

Vest4

0.27

GERP RS

-8.0

Mutation Taster

=185/15

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.58

Position offset: 24

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over