6-32756412-C-T

Variant names:

• chr6-32756412-C-T
• rs7774954
• NM_001300790.2:c.*41G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001300790.2(HLA-DQB2):​c.*41G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,240,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 22 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.*41G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000437316.7	NP_001287719.1
HLA-DQB2	NM_001198858.2	c.*41G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001185787.1
HLA-DQB2	XM_011514560.3	c.*41G>A		3_prime_UTR_variant	Exon 5 of 5		XP_011512862.1
HLA-DQB2	XM_011514561.4	c.*41G>A		3_prime_UTR_variant	Exon 4 of 4		XP_011512863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.*41G>A		3_prime_UTR_variant	Exon 6 of 6	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.*822G>A		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.*41G>A		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.*41G>A		3_prime_UTR_variant	Exon 4 of 4	6		ENSP00000415997.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152000 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.19e-7 AC: 1 AN: 1088196 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 554192

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25480

American (AMR) AF: 0.00 AC: 0 AN: 39306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23370

East Asian (EAS) AF: 0.00 AC: 0 AN: 36580

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4972

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 784526

Other (OTH) AF: 0.00 AC: 0 AN: 48016

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152000 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41298

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.42
PhyloP100		0.063

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: rs7774954; hg19: chr6-32724189;