chr6-32756140-C-T

Position:

• chr6-32756140-C-T

Variant summary

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

The NM_001300790.2(HLA-DQB2):​c.*313G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 421,676 control chromosomes in the GnomAD database, including 58,260 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 0.50 (19803 hom., cov: 32)
  • Exomes 𝑓: 0.52 (38457 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913

Genes affected

HLA-DQB2 (HGNC:4945): (major histocompatibility complex, class II, DQ beta 2) HLA-DQB2 belongs to the family of HLA class II beta chain paralogs. Class II molecules are heterodimers consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. They play a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). Polymorphisms in the alpha and beta chains specify the peptide binding specificity, and typing for these polymorphisms is routinely done for bone marrow transplantation. However this gene, HLA-DQB2, is not routinely typed, as it is not thought to have an effect on transplantation. There is conflicting evidence in the literature and public sequence databases for the protein-coding capacity of HLA-DQB2. Because there is evidence of transcription and an intact ORF, HLA-DQB2 is represented in Entrez Gene and in RefSeq as a protein-coding locus. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.*313G>A		3_prime_UTR_variant	6/6	ENST00000437316.7	NP_001287719.1
HLA-DQB2	NM_001198858.2	c.*313G>A		3_prime_UTR_variant	5/5		NP_001185787.1
HLA-DQB2	XM_011514560.3	c.*313G>A		3_prime_UTR_variant	5/5		XP_011512862.1
HLA-DQB2	XM_011514561.4	c.*313G>A		3_prime_UTR_variant	4/4		XP_011512863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.*313G>A		3_prime_UTR_variant	6/6		NM_001300790.2	ENSP00000396330	P1
HLA-DQB2	ENST00000411527.5	c.*313G>A		3_prime_UTR_variant	5/5			ENSP00000390431
HLA-DQB2	ENST00000435145.6	c.*1094G>A		3_prime_UTR_variant	5/5			ENSP00000410512

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75753 AN: 151908 Hom.: 19773 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.522 AC: 140818 AN: 269648 Hom.: 38457 Cov.: 0 AF XY: 0.527 AC XY: 72900 AN XY: 138254

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.601

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.499 AC: 75843 AN: 152028 Hom.: 19803 Cov.: 32 AF XY: 0.509 AC XY: 37827 AN XY: 74334

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.529

Alfa AF: 0.503 Hom.: 18480

Bravo AF: 0.491

Asia WGS AF: 0.705 AC: 2446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.75

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: rs7756516; hg19: chr6-32723917;