chr6-32762044-C-A

Position:

• chr6-32762044-C-A

Variant summary

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

The NM_001300790.2(HLA-DQB2):​c.98-118G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,340,726 control chromosomes in the GnomAD database, including 236,528 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 (31622 hom., cov: 32)
  • Exomes 𝑓: 0.58 (204906 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.98-118G>T		intron_variant		ENST00000437316.7	NP_001287719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.98-118G>T		intron_variant			NM_001300790.2	ENSP00000396330	P1
HLA-DQB2	ENST00000411527.5	c.98-118G>T		intron_variant				ENSP00000390431
HLA-DQB2	ENST00000427449.1	c.94-118G>T		intron_variant				ENSP00000415997
HLA-DQB2	ENST00000435145.6	c.98-118G>T		intron_variant				ENSP00000410512

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96995 AN: 151858 Hom.: 31575 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.578 AC: 687502 AN: 1188750 Hom.: 204906 AF XY: 0.586 AC XY: 345394 AN XY: 589200

Gnomad4 AFR exome AF: 0.683

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.784

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.602

GnomAD4 genome AF: 0.639 AC: 97103 AN: 151976 Hom.: 31622 Cov.: 32 AF XY: 0.646 AC XY: 48013 AN XY: 74290

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.698

Alfa AF: 0.548 Hom.: 5240

Bravo AF: 0.651

Asia WGS AF: 0.820 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.60

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: rs7768538; hg19: chr6-32729821;