rs9276442

Positions:

• chr6-32747124-C-T

Variant summary

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

The NM_020056.5(HLA-DQA2):​c.*563C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 157,292 control chromosomes in the GnomAD database, including 1,607 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 (1588 hom., cov: 27)
  • Exomes 𝑓: 0.046 (19 hom.)
• Consequence: HLA-DQA2 NM_020056.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.*563C>T		3_prime_UTR_variant	5/5	ENST00000374940.4	NP_064440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.*563C>T		3_prime_UTR_variant	5/5	6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17080 AN: 149116 Hom.: 1586 Cov.: 27

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0774

Gnomad EAS AF: 0.00566

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00505

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0463 AC: 374 AN: 8076 Hom.: 19 Cov.: 0 AF XY: 0.0430 AC XY: 187 AN XY: 4352

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.0323

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.00862

Gnomad4 NFE exome AF: 0.0419

Gnomad4 OTH exome AF: 0.0786

GnomAD4 genome AF: 0.115 AC: 17088 AN: 149216 Hom.: 1588 Cov.: 27 AF XY: 0.110 AC XY: 8016 AN XY: 72696

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0774

Gnomad4 EAS AF: 0.00548

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.00505

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0820 Hom.: 207

Bravo AF: 0.137

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs9276442; hg19: chr6-32714901;