6-32762044-C-A

Variant names:

• chr6-32762044-C-A
• rs7768538
• NM_001300790.2:c.98-118G>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.98-118G>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
• Publications: 21 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=-0.9).
• 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 rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.98-118G>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.98-118G>T		intron_variant	Intron 1 of 5	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.98-118G>T		intron_variant	Intron 1 of 4	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.98-118G>T		intron_variant	Intron 1 of 4	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.92-118G>T		intron_variant	Intron 1 of 3	6		ENSP00000415997.1

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

African (AFR) AF: 0.683 AC: 17644 AN: 25844

American (AMR) AF: 0.729 AC: 18830 AN: 25818

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 13979 AN: 20598

East Asian (EAS) AF: 0.846 AC: 29132 AN: 34426

South Asian (SAS) AF: 0.784 AC: 53162 AN: 67848

European-Finnish (FIN) AF: 0.573 AC: 24012 AN: 41924

Middle Eastern (MID) AF: 0.731 AC: 2550 AN: 3488

European-Non Finnish (NFE) AF: 0.542 AC: 497911 AN: 918530

Other (OTH) AF: 0.602 AC: 30282 AN: 50274

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

African (AFR) AF: 0.688 AC: 28510 AN: 41436

American (AMR) AF: 0.696 AC: 10632 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3466

East Asian (EAS) AF: 0.874 AC: 4507 AN: 5156

South Asian (SAS) AF: 0.815 AC: 3927 AN: 4820

European-Finnish (FIN) AF: 0.583 AC: 6165 AN: 10580

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38690 AN: 67920

Other (OTH) AF: 0.698 AC: 1475 AN: 2112

Alfa AF: 0.599 Hom.: 11728

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
PhyloP100		-0.015
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: rs7768538; hg19: chr6-32729821;