6-32744470-T-C

Variant names:

• chr6-32744470-T-C
• rs9276431
• NM_020056.5:c.83-689T>C

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.83-689T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 150,658 control chromosomes in the GnomAD database, including 29,191 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 (29191 hom., cov: 30)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 26 publications found

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.83-689T>C		intron_variant	Intron 1 of 4	ENST00000374940.4	NP_064440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA2	ENST00000374940.4	c.83-689T>C		intron_variant	Intron 1 of 4	6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.620 AC: 93338 AN: 150538 Hom.: 29149 Cov.: 30

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.620 AC: 93437 AN: 150658 Hom.: 29191 Cov.: 30 AF XY: 0.626 AC XY: 46124 AN XY: 73626

African (AFR) AF: 0.637 AC: 26158 AN: 41064

American (AMR) AF: 0.685 AC: 10354 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2298 AN: 3434

East Asian (EAS) AF: 0.845 AC: 4345 AN: 5140

South Asian (SAS) AF: 0.792 AC: 3769 AN: 4760

European-Finnish (FIN) AF: 0.576 AC: 5944 AN: 10314

Middle Eastern (MID) AF: 0.697 AC: 202 AN: 290

European-Non Finnish (NFE) AF: 0.567 AC: 38280 AN: 67538

Other (OTH) AF: 0.683 AC: 1424 AN: 2086

Alfa AF: 0.586 Hom.: 78198

Bravo AF: 0.635

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.56
PhyloP100		-0.71
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

Other links and lift over

dbSNP: rs9276431; hg19: chr6-32712247;