6-32759025-CCG-TAA

Variant names:

• chr6-32759025-CCG-TAA
• NM_001300790.2:c.469_471delCGGinsTTA
• HLA-DQB2 p.Arg157Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001300790.2(HLA-DQB2):​c.469_471delCGGinsTTA​(p.Arg157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 38)
• Consequence: HLA-DQB2 NM_001300790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.469_471delCGGinsTTA	p.Arg157Leu	missense	N/A	NP_001287719.1	Q5SR05
	HLA-DQB2	NM_001198858.2		c.469_471delCGGinsTTA	p.Arg157Leu	missense	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.469_471delCGGinsTTA	p.Arg157Leu	missense	N/A	ENSP00000396330.2	Q5SR05
	HLA-DQB2	ENST00000435145.6	TSL:6	c.469_471delCGGinsTTA	p.Arg157Leu	missense	N/A	ENSP00000410512.2	A2ADX3
	HLA-DQB2	ENST00000870921.1		c.469_471delCGGinsTTA	p.Arg157Leu	missense	N/A	ENSP00000540980.1

Frequencies

GnomAD3 genomes Cov.: 38

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

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-32726802;