NM_020056.5:c.83-832G>A

Variant names:

• chr6-32744327-G-A
• rs9276429
• NM_020056.5:c.83-832G>A

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.83-832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 148,222 control chromosomes in the GnomAD database, including 30,058 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 0.64 (30058 hom., cov: 31)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 20 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.83-832G>A		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.83-832G>A		intron_variant	Intron 1 of 4	6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 94700 AN: 148106 Hom.: 30018 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.640 AC: 94796 AN: 148222 Hom.: 30058 Cov.: 31 AF XY: 0.646 AC XY: 46832 AN XY: 72532

African (AFR) AF: 0.650 AC: 26525 AN: 40780

American (AMR) AF: 0.699 AC: 10568 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2342 AN: 3378

East Asian (EAS) AF: 0.850 AC: 4399 AN: 5178

South Asian (SAS) AF: 0.801 AC: 3851 AN: 4810

European-Finnish (FIN) AF: 0.597 AC: 6085 AN: 10198

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.591 AC: 38701 AN: 65492

Other (OTH) AF: 0.698 AC: 1451 AN: 2078

Alfa AF: 0.645 Hom.: 19104

Asia WGS AF: 0.795 AC: 2760 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	1.0
DANN	Benign	0.74
PhyloP100		0.0070
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: rs9276429; hg19: chr6-32712104;