rs2239800

Positions:

• chr6-32745490-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020056.5(HLA-DQA2):​c.331+83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,435,500 control chromosomes in the GnomAD database, including 11,845 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 0.11 (1177 hom., cov: 30)
  • Exomes 𝑓: 0.11 (10668 hom.)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA2	NM_020056.5	c.331+83A>G		intron_variant		ENST00000374940.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.331+83A>G		intron_variant			NM_020056.5	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16808 AN: 150278 Hom.: 1180 Cov.: 30

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.108 AC: 138304 AN: 1285102 Hom.: 10668 AF XY: 0.109 AC XY: 70080 AN XY: 644288

Gnomad4 AFR exome AF: 0.0703

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.112 AC: 16815 AN: 150398 Hom.: 1177 Cov.: 30 AF XY: 0.116 AC XY: 8482 AN XY: 73434

Gnomad4 AFR AF: 0.0680

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0922

Gnomad4 OTH AF: 0.115

Alfa AF: 0.111 Hom.: 2226

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2239800; hg19: chr6-32713267; COSMIC: COSV66564889; COSMIC: COSV66564889;