rs9276439

Variant names:

• chr6-32746826-C-T
• rs9276439
• NM_020056.5:c.*265C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020056.5(HLA-DQA2):​c.*265C>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 0.0811 in 369,872 control chromosomes in the GnomAD database, including 2,160 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 (1532 hom., cov: 32)
  • Exomes 𝑓: 0.057 (628 hom.)
• Consequence: HLA-DQA2 NM_020056.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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 rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.*265C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000374940.4	NP_064440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.*265C>T		3_prime_UTR_variant	Exon 5 of 5	6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17536 AN: 151896 Hom.: 1531 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.0572 AC: 12471 AN: 217858 Hom.: 628 Cov.: 0 AF XY: 0.0518 AC XY: 6243 AN XY: 120610

Gnomad4 AFR exome AF: 0.250 AC: 1452 AN: 5806

Gnomad4 AMR exome AF: 0.0952 AC: 1175 AN: 12336

Gnomad4 ASJ exome AF: 0.0782 AC: 398 AN: 5088

Gnomad4 EAS exome AF: 0.00146 AC: 13 AN: 8922

Gnomad4 SAS exome AF: 0.0193 AC: 805 AN: 41636

Gnomad4 FIN exome AF: 0.00992 AC: 89 AN: 8968

Gnomad4 NFE exome AF: 0.0633 AC: 7716 AN: 121942

Gnomad4 Remaining exome AF: 0.0628 AC: 677 AN: 10778

GnomAD4 genome AF: 0.115 AC: 17542 AN: 152014 Hom.: 1532 Cov.: 32 AF XY: 0.111 AC XY: 8242 AN XY: 74342

Gnomad4 AFR AF: 0.248 AC: 0.248283 AN: 0.248283

Gnomad4 AMR AF: 0.128 AC: 0.127784 AN: 0.127784

Gnomad4 ASJ AF: 0.0781 AC: 0.078143 AN: 0.078143

Gnomad4 EAS AF: 0.00540 AC: 0.00540332 AN: 0.00540332

Gnomad4 SAS AF: 0.0151 AC: 0.0151264 AN: 0.0151264

Gnomad4 FIN AF: 0.00509 AC: 0.00509146 AN: 0.00509146

Gnomad4 NFE AF: 0.0668 AC: 0.0667765 AN: 0.0667765

Gnomad4 OTH AF: 0.145 AC: 0.144886 AN: 0.144886

Alfa AF: 0.139 Hom.: 739

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	-0.94
CADD	Benign	6.1
DANN	Benign	0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs9276439; hg19: chr6-32714603;