rs1049110

Positions:

• chr6-32759026-C-A
• chr6-32759026-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300790.2(HLA-DQB2):​c.470G>T​(p.Arg157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R157Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 38)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33186808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.470G>T	p.Arg157Leu	missense_variant	3/6	ENST00000437316.7	NP_001287719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.470G>T	p.Arg157Leu	missense_variant	3/6		NM_001300790.2	ENSP00000396330	P1
HLA-DQB2	ENST00000435145.6	c.470G>T	p.Arg157Leu	missense_variant	3/5			ENSP00000410512
HLA-DQB2	ENST00000411527.5	c.470G>T	p.Arg157Leu	missense_variant	3/5			ENSP00000390431
HLA-DQB2	ENST00000427449.1	c.467G>T	p.Arg156Leu	missense_variant	3/4			ENSP00000415997

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452002 Hom.: 0 Cov.: 90 AF XY: 0.00000138 AC XY: 1 AN XY: 722366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.85	.;P;.
Vest4		0.43
MutPred		0.65		Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);
MVP		0.28
MPC		1.4
ClinPred		0.93	D
GERP RS		-2.2
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1049110; hg19: chr6-32726803;