rs3208181

chr6-32745253-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020056.5(HLA-DQA2):c.177T>C(p.Tyr59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,595,902 control chromosomes in the GnomAD database, including 252,806 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 0.58 (22996 hom., cov: 30)
  • Exomes 𝑓: 0.57 (229810 hom.)
• Consequence: HLA-DQA2 NM_020056.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA2	NM_020056.5	c.177T>C	p.Tyr59=	synonymous_variant	2/5	ENST00000374940.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.177T>C	p.Tyr59=	synonymous_variant	2/5		NM_020056.5	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 84939 AN: 147010 Hom.: 22967 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.633

GnomAD3 exomes AF: 0.626 AC: 156313 AN: 249618 Hom.: 49741 AF XY: 0.626 AC XY: 84584 AN XY: 135072

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.830

Gnomad SAS exome AF: 0.660

Gnomad FIN exome AF: 0.572

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.623

GnomAD4 exome AF: 0.565 AC: 819089 AN: 1448778 Hom.: 229810 Cov.: 47 AF XY: 0.568 AC XY: 409621 AN XY: 720728

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.654

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.578 AC: 85025 AN: 147124 Hom.: 22996 Cov.: 30 AF XY: 0.583 AC XY: 41900 AN XY: 71854

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.638

Alfa AF: 0.573 Hom.: 10466

Asia WGS AF: 0.667 AC: 2317 AN: 3478

EpiCase AF: 0.600

EpiControl AF: 0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.11
Dann	Benign	0.31

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

Other links and lift over

dbSNP: rs3208181; hg19: chr6-32713030; COSMIC: COSV66566017; COSMIC: COSV66566017;