rs9276438

chr6-32746739-G-A

Variant summary

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

The NM_020056.5(HLA-DQA2):c.*178G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 543,766 control chromosomes in the GnomAD database, including 2,737 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 0.12 (1536 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1201 hom.)
• Consequence: HLA-DQA2 NM_020056.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA2	NM_020056.5	c.*178G>A		3_prime_UTR_variant	5/5	ENST00000374940.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.*178G>A		3_prime_UTR_variant	5/5		NM_020056.5	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17562 AN: 151736 Hom.: 1535 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.0604 AC: 23674 AN: 391912 Hom.: 1201 Cov.: 0 AF XY: 0.0559 AC XY: 12106 AN XY: 216578

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0923

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.0205

Gnomad4 FIN exome AF: 0.00863

Gnomad4 NFE exome AF: 0.0641

Gnomad4 OTH exome AF: 0.0739

GnomAD4 genome AF: 0.116 AC: 17568 AN: 151854 Hom.: 1536 Cov.: 32 AF XY: 0.111 AC XY: 8244 AN XY: 74234

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.0146

Gnomad4 FIN AF: 0.00520

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0993 Hom.: 224

Bravo AF: 0.137

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.45
Dann	Benign	0.45

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: rs9276438; hg19: chr6-32714516;