6-32746090-C-T

Position:

• chr6-32746090-C-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.613+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,603,848 control chromosomes in the GnomAD database, including 18,921 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 0.12 (778 hom., cov: 35)
  • Exomes 𝑓: 0.17 (18143 hom.)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA2	NM_020056.5	c.613+18C>T		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.613+18C>T		intron_variant		6	NM_020056.5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18844 AN: 151530 Hom.: 777 Cov.: 35

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.133 AC: 32790 AN: 245916 Hom.: 2377 AF XY: 0.137 AC XY: 18399 AN XY: 134062

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.0639

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.0211

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.169 AC: 245381 AN: 1452198 Hom.: 18143 Cov.: 66 AF XY: 0.168 AC XY: 121184 AN XY: 722554

Gnomad4 AFR exome AF: 0.0518

Gnomad4 AMR exome AF: 0.0666

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0158

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.124 AC: 18837 AN: 151650 Hom.: 778 Cov.: 35 AF XY: 0.123 AC XY: 9108 AN XY: 74158

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.119

Alfa AF: 0.158 Hom.: 1574

Asia WGS AF: 0.0700 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.84

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: rs9276435; hg19: chr6-32713867; COSMIC: COSV66565222; COSMIC: COSV66565222;