6-32757416-A-G

Variant names:

• chr6-32757416-A-G
• rs2301271
• NM_001300790.2:c.758-112T>C

Variant summary

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

The NM_001300790.2(HLA-DQB2):​c.758-112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 793,134 control chromosomes in the GnomAD database, including 144,660 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 0.61 (27833 hom., cov: 31)
  • Exomes 𝑓: 0.59 (116827 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.758-112T>C		intron_variant	Intron 4 of 5	ENST00000437316.7	NP_001287719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.758-112T>C		intron_variant	Intron 4 of 5	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.758-112T>C		intron_variant	Intron 4 of 4	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.647-112T>C		intron_variant	Intron 3 of 4	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.641-950T>C		intron_variant	Intron 3 of 3	6		ENSP00000415997.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 91167 AN: 148784 Hom.: 27800 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.593 AC: 381936 AN: 644234 Hom.: 116827 AF XY: 0.602 AC XY: 204074 AN XY: 339224

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.717

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.561

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.613 AC: 91255 AN: 148900 Hom.: 27833 Cov.: 31 AF XY: 0.620 AC XY: 45116 AN XY: 72810

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.669

Alfa AF: 0.594 Hom.: 45361

Asia WGS AF: 0.783 AC: 2719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2301271; hg19: chr6-32725193;