Genetic Variant NM_002122.5:c.250G>C (chr6-32641477-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002122.5(HLA-DQA1):c.250G>C(p.Gly84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 931,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 13)

Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

HLA-DQA1
NM_002122.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.47

Publications

0 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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36232507).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	NM_002122.5	MANE Select	c.250G>C	p.Gly84Arg	missense	Exon 2 of 5	NP_002113.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.250G>C	p.Gly84Arg	missense	Exon 2 of 5	ENSP00000339398.5
HLA-DQA1	ENST00000374949.2	TSL:6	c.250G>C	p.Gly84Arg	missense	Exon 2 of 4	ENSP00000364087.2
HLA-DQA1	ENST00000395363.5	TSL:6	c.250G>C	p.Gly84Arg	missense	Exon 2 of 5	ENSP00000378767.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

931910

Hom.:

Cov.:

AF XY:

0.00000428

AC XY:

AN XY:

467042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24234

American (AMR)

AF:

0.00

AC:

AN:

19362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15448

East Asian (EAS)

AF:

0.00

AC:

AN:

26254

South Asian (SAS)

AF:

0.00

AC:

AN:

62734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3280

European-Non Finnish (NFE)

AF:

0.00000285

AC:

AN:

702594

Other (OTH)

AF:

0.00

AC:

AN:

39272

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.012

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.59

M_CAP

Benign

0.0037

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.99

PhyloP100

2.5

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.21

Sift

Uncertain

0.013

Sift4G

Benign

0.11

Vest4

0.39

MutPred

0.57

Gain of MoRF binding (P = 0.0213)

MVP

0.088

MPC

1.0

ClinPred

0.17

GERP RS

2.1

gMVP

0.62

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over