6-32757416-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 66 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	NM_001300790.2	MANE Select	c.758-112T>C		intron	N/A	NP_001287719.1	Q5SR05
	HLA-DQB2	NM_001198858.2		c.647-112T>C		intron	N/A	NP_001185787.1	P05538-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	ENST00000437316.7	TSL:6 MANE Select	c.758-112T>C		intron	N/A	ENSP00000396330.2	Q5SR05
	HLA-DQB2	ENST00000435145.6	TSL:6	c.758-112T>C		intron	N/A	ENSP00000410512.2	A2ADX3
	HLA-DQB2	ENST00000870921.1		c.757+357T>C		intron	N/A	ENSP00000540980.1

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

African (AFR) AF: 0.629 AC: 10439 AN: 16592

American (AMR) AF: 0.717 AC: 21858 AN: 30486

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 12081 AN: 18204

East Asian (EAS) AF: 0.819 AC: 26265 AN: 32082

South Asian (SAS) AF: 0.754 AC: 43008 AN: 57038

European-Finnish (FIN) AF: 0.561 AC: 23441 AN: 41788

Middle Eastern (MID) AF: 0.670 AC: 2712 AN: 4048

European-Non Finnish (NFE) AF: 0.541 AC: 222319 AN: 411020

Other (OTH) AF: 0.601 AC: 19813 AN: 32976

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

African (AFR) AF: 0.635 AC: 25593 AN: 40280

American (AMR) AF: 0.676 AC: 10085 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2253 AN: 3414

East Asian (EAS) AF: 0.843 AC: 4285 AN: 5086

South Asian (SAS) AF: 0.766 AC: 3530 AN: 4608

European-Finnish (FIN) AF: 0.576 AC: 6017 AN: 10452

Middle Eastern (MID) AF: 0.682 AC: 195 AN: 286

European-Non Finnish (NFE) AF: 0.557 AC: 37271 AN: 66906

Other (OTH) AF: 0.669 AC: 1373 AN: 2052

Alfa AF: 0.589 Hom.: 107141

Asia WGS AF: 0.783 AC: 2719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.55
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301271; hg19: chr6-32725193;