Variant 6-32745222-C-G 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.146C>G(p.Thr49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 0 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: 0.880

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=0.03749454).

BP6

Variant 6-32745222-C-G is Benign according to our data. Variant chr6-32745222-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2681314.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.146C>G	p.Thr49Ser	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.146C>G	p.Thr49Ser	missense_variant	2/5		NM_020056.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

799

AN:

136936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00252

Gnomad AMI

AF:

0.00622

Gnomad AMR

AF:

0.00758

Gnomad ASJ

AF:

0.00822

Gnomad EAS

AF:

0.0219

Gnomad SAS

AF:

0.00242

Gnomad FIN

AF:

0.00858

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.00368

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000531

AC:

754

AN:

1419348

Hom.:

Cov.:

AF XY:

0.000651

AC XY:

458

AN XY:

703966

show subpopulations

Gnomad4 AFR exome

AF:

0.000213

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.000568

Gnomad4 EAS exome

AF:

0.00232

Gnomad4 SAS exome

AF:

0.000205

Gnomad4 FIN exome

AF:

0.00344

Gnomad4 NFE exome

AF:

0.000332

Gnomad4 OTH exome

AF:

0.000599

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00585

AC:

802

AN:

137018

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

403

AN XY:

66902

show subpopulations

Gnomad4 AFR

AF:

0.00252

Gnomad4 AMR

AF:

0.00772

Gnomad4 ASJ

AF:

0.00822

Gnomad4 EAS

AF:

0.0219

Gnomad4 SAS

AF:

0.00264

Gnomad4 FIN

AF:

0.00858

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.00364

Alfa

AF:

0.0305

Hom.:

ExAC

AF:

0.000972

AC:

118

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

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.14

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.6

REVEL

Benign

0.12

Sift

Benign

0.10

Sift4G

Benign

0.17

Polyphen

0.016

Vest4

0.35

MutPred

0.38

Loss of phosphorylation at T49 (P = 0.0467);

MVP

0.21

MPC

0.41

ClinPred

0.023

GERP RS

3.2

Varity_R

0.090

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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