6-32744005-A-G

Position:

• chr6-32744005-A-G

Variant summary

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

The NM_020056.5(HLA-DQA2):​c.83-1154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,006 control chromosomes in the GnomAD database, including 11,947 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 0.38 (11947 hom., cov: 32)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.83-1154A>G		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.83-1154A>G		intron_variant		6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57062 AN: 151888 Hom.: 11938 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.376 AC: 57104 AN: 152006 Hom.: 11947 Cov.: 32 AF XY: 0.384 AC XY: 28547 AN XY: 74274

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.376

Alfa AF: 0.411 Hom.: 2356

Bravo AF: 0.362

Asia WGS AF: 0.547 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.46

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: rs2227127; hg19: chr6-32711782;