Variant 6-32745293-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_020056.5(HLA-DQA2):c.217A>C(p.Met73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00013 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DQA2
NM_020056.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.52

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 made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040393054).

BP6

Variant 6-32745293-A-C is Benign according to our data. Variant chr6-32745293-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2681313.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA2	NM_020056.5 linkuse as main transcript	c.217A>C	p.Met73Leu	missense_variant	2/5	ENST00000374940.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA2	ENST00000374940.4 linkuse as main transcript	c.217A>C	p.Met73Leu	missense_variant	2/5		NM_020056.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1751

AN:

123438

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00885

Gnomad AMI

AF:

0.0279

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.0251

Gnomad SAS

AF:

0.0158

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250438

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000134

AC:

190

AN:

1422528

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

706240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000240

Gnomad4 ASJ exome

AF:

0.000160

Gnomad4 EAS exome

AF:

0.000131

Gnomad4 SAS exome

AF:

0.000260

Gnomad4 FIN exome

AF:

0.00192

Gnomad4 NFE exome

AF:

0.0000514

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0142

AC:

1754

AN:

123530

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

839

AN XY:

60596

show subpopulations

Gnomad4 AFR

AF:

0.00888

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.0252

Gnomad4 SAS

AF:

0.0158

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0200

Hom.:

ExAC

AF:

0.000437

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma

Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.048

DANN

Benign

0.34

DEOGEN2

Benign

0.0013

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0035

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.18

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.86

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.19

MutPred

0.48

Gain of catalytic residue at M73 (P = 0.0059);

MVP

0.099

MPC

0.38

ClinPred

0.032

GERP RS

-6.1

Varity_R

0.10

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over