6-32759026-C-T

Variant names:

• chr6-32759026-C-T
• rs1049110
• NM_001300790.2:c.470G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001300790.2(HLA-DQB2):​c.470G>A​(p.Arg157Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (5106 hom., cov: 38)
  • Exomes 𝑓: 0.43 (40811 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB2 NM_001300790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 38 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030323267).

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.470G>A	p.Arg157Gln	missense	Exon 3 of 6	NP_001287719.1	Q5SR05
	HLA-DQB2	NM_001198858.2		c.470G>A	p.Arg157Gln	missense	Exon 3 of 5	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.470G>A	p.Arg157Gln	missense	Exon 3 of 6	ENSP00000396330.2	Q5SR05
	HLA-DQB2	ENST00000435145.6	TSL:6	c.470G>A	p.Arg157Gln	missense	Exon 3 of 5	ENSP00000410512.2	A2ADX3
	HLA-DQB2	ENST00000870921.1		c.470G>A	p.Arg157Gln	missense	Exon 3 of 5	ENSP00000540980.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 67667 AN: 148558 Hom.: 5094 Cov.: 38

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.510 AC: 124078 AN: 243062 AF XY: 0.508

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.526

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.435 AC: 629487 AN: 1447966 Hom.: 40811 Cov.: 90 AF XY: 0.437 AC XY: 314866 AN XY: 720392

African (AFR) AF: 0.472 AC: 15651 AN: 33150

American (AMR) AF: 0.487 AC: 21567 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 12323 AN: 25914

East Asian (EAS) AF: 0.540 AC: 21003 AN: 38906

South Asian (SAS) AF: 0.496 AC: 42328 AN: 85288

European-Finnish (FIN) AF: 0.460 AC: 24309 AN: 52818

Middle Eastern (MID) AF: 0.468 AC: 2678 AN: 5718

European-Non Finnish (NFE) AF: 0.420 AC: 463087 AN: 1102034

Other (OTH) AF: 0.443 AC: 26541 AN: 59874

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.456 AC: 67735 AN: 148670 Hom.: 5106 Cov.: 38 AF XY: 0.460 AC XY: 33341 AN XY: 72550

African (AFR) AF: 0.470 AC: 19023 AN: 40466

American (AMR) AF: 0.477 AC: 7100 AN: 14872

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1582 AN: 3394

East Asian (EAS) AF: 0.549 AC: 2689 AN: 4902

South Asian (SAS) AF: 0.506 AC: 2350 AN: 4646

European-Finnish (FIN) AF: 0.459 AC: 4744 AN: 10336

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.429 AC: 28667 AN: 66838

Other (OTH) AF: 0.481 AC: 985 AN: 2046

Alfa AF: 0.489 Hom.: 1777

ExAC AF: 0.469 AC: 56712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.84
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.047
Sift	Benign	0.15	T
Sift4G	Uncertain	0.045	D
Polyphen		0.23	B
Vest4		0.13
MPC		0.63
ClinPred		0.012	T
GERP RS		-2.2
gMVP		0.39
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: rs1049110; hg19: chr6-32726803; COSMIC: COSV68614539;