6-32747006-A-T

Position:

• chr6-32747006-A-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.*445A>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 0.611 in 256,948 control chromosomes in the GnomAD database, including 49,145 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 0.62 (29279 hom., cov: 29)
  • Exomes 𝑓: 0.60 (19866 hom.)
• Consequence: HLA-DQA2 NM_020056.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.*445A>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.*445A>T		3_prime_UTR_variant	5/5	6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93466 AN: 151582 Hom.: 29242 Cov.: 29

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.671

GnomAD4 exome AF: 0.603 AC: 63442 AN: 105246 Hom.: 19866 Cov.: 0 AF XY: 0.614 AC XY: 34075 AN XY: 55516

Gnomad4 AFR exome AF: 0.631

Gnomad4 AMR exome AF: 0.702

Gnomad4 ASJ exome AF: 0.645

Gnomad4 EAS exome AF: 0.817

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.617 AC: 93562 AN: 151702 Hom.: 29279 Cov.: 29 AF XY: 0.622 AC XY: 46125 AN XY: 74128

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.676

Alfa AF: 0.449 Hom.: 1164

Bravo AF: 0.630

Asia WGS AF: 0.725 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.0
DANN	Benign	0.42

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: rs9276440; hg19: chr6-32714783;