6-32743878-G-C

Position:

• chr6-32743878-G-C

Variant summary

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

The NM_020056.5(HLA-DQA2):​c.83-1281G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,522 control chromosomes in the GnomAD database, including 23,699 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 0.55 (23699 hom., cov: 30)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.83-1281G>C		intron_variant		ENST00000374940.4	NP_064440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.83-1281G>C		intron_variant			NM_020056.5	ENSP00000364076	P1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83754 AN: 151402 Hom.: 23666 Cov.: 30

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.553 AC: 83849 AN: 151522 Hom.: 23699 Cov.: 30 AF XY: 0.559 AC XY: 41369 AN XY: 74040

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.612

Alfa AF: 0.566 Hom.: 13047

Asia WGS AF: 0.681 AC: 2364 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	0.21
DANN	Benign	0.54

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: rs2213567; hg19: chr6-32711655;