6-32763481-G-T

Variant names:

• chr6-32763481-G-T
• rs1573649
• NM_001300790.2:c.-11C>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.-11C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,036 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 0 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=-0.87).

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.-11C>A		5_prime_UTR	Exon 1 of 6	NP_001287719.1
	HLA-DQB2	NM_001198858.2		c.-11C>A		5_prime_UTR	Exon 1 of 5	NP_001185787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	ENST00000437316.7	TSL:6 MANE Select	c.-11C>A		5_prime_UTR	Exon 1 of 6	ENSP00000396330.2
	HLA-DQB2	ENST00000435145.6	TSL:6	c.-11C>A		5_prime_UTR	Exon 1 of 5	ENSP00000410512.2
	HLA-DQB2	ENST00000870921.1		c.-11C>A		5_prime_UTR	Exon 1 of 5	ENSP00000540980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387036 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 685166

African (AFR) AF: 0.00 AC: 0 AN: 31652

American (AMR) AF: 0.00 AC: 0 AN: 35820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25112

East Asian (EAS) AF: 0.00 AC: 0 AN: 36240

South Asian (SAS) AF: 0.00 AC: 0 AN: 79024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067422

Other (OTH) AF: 0.00 AC: 0 AN: 57652

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.40
PhyloP100		-0.71
PromoterAI		-0.079	Neutral

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: rs1573649; hg19: chr6-32731258;