NM_001300790.2:c.98-383C>T

Variant names:

• chr6-32762309-G-A
• rs2051549
• NM_001300790.2:c.98-383C>T

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.98-383C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,022 control chromosomes in the GnomAD database, including 32,153 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 (32153 hom., cov: 32)
• Consequence: HLA-DQB2 NM_001300790.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 55 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=-1.0).
• 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 rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.98-383C>T		intron_variant	Intron 1 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.98-383C>T		intron_variant	Intron 1 of 5	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.98-383C>T		intron_variant	Intron 1 of 4	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.98-383C>T		intron_variant	Intron 1 of 4	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.92-383C>T		intron_variant	Intron 1 of 3	6		ENSP00000415997.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97784 AN: 151904 Hom.: 32109 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.696

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.644 AC: 97889 AN: 152022 Hom.: 32153 Cov.: 32 AF XY: 0.651 AC XY: 48384 AN XY: 74300

African (AFR) AF: 0.704 AC: 29179 AN: 41456

American (AMR) AF: 0.698 AC: 10646 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2328 AN: 3466

East Asian (EAS) AF: 0.874 AC: 4528 AN: 5178

South Asian (SAS) AF: 0.815 AC: 3928 AN: 4818

European-Finnish (FIN) AF: 0.584 AC: 6165 AN: 10560

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38762 AN: 67964

Other (OTH) AF: 0.700 AC: 1479 AN: 2112

Alfa AF: 0.595 Hom.: 92233

Bravo AF: 0.656

Asia WGS AF: 0.822 AC: 2852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.5
DANN	Benign	0.41
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2051549; hg19: chr6-32730086;