6-32761836-T-C

Position:

• chr6-32761836-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001300790.2(HLA-DQB2):​c.188A>G​(p.Glu63Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,608,320 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (5 hom., cov: 34)
  • Exomes 𝑓: 0.0086 (77 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.35

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009718716).
• BP6: Variant 6-32761836-T-C is Benign according to our data. Variant chr6-32761836-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.188A>G	p.Glu63Gly	missense_variant	2/6	ENST00000437316.7	NP_001287719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.188A>G	p.Glu63Gly	missense_variant	2/6	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.188A>G	p.Glu63Gly	missense_variant	2/5	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.188A>G	p.Glu63Gly	missense_variant	2/5	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.182A>G	p.Glu61Gly	missense_variant	2/4	6		ENSP00000415997.1

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 993 AN: 152202 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00910

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00793 AC: 1890 AN: 238298 Hom.: 16 AF XY: 0.00805 AC XY: 1041 AN XY: 129338

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.0329

Gnomad EAS exome AF: 0.00125

Gnomad SAS exome AF: 0.00533

Gnomad FIN exome AF: 0.00508

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.00865 AC: 12589 AN: 1456000 Hom.: 77 Cov.: 71 AF XY: 0.00869 AC XY: 6287 AN XY: 723770

Gnomad4 AFR exome AF: 0.00400

Gnomad4 AMR exome AF: 0.00272

Gnomad4 ASJ exome AF: 0.0304

Gnomad4 EAS exome AF: 0.000635

Gnomad4 SAS exome AF: 0.00535

Gnomad4 FIN exome AF: 0.00512

Gnomad4 NFE exome AF: 0.00922

Gnomad4 OTH exome AF: 0.00841

GnomAD4 genome AF: 0.00653 AC: 995 AN: 152320 Hom.: 5 Cov.: 34 AF XY: 0.00630 AC XY: 469 AN XY: 74482

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.00910

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0100 Hom.: 18

Bravo AF: 0.00640

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00986 AC: 38

ExAC AF: 0.00792 AC: 961

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

HLA-DQB2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	.;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.75	D
MetaRNN	Benign	0.0097	T;T;T
MetaSVM	Benign	-0.78	T
PROVEAN	Pathogenic	-6.7	D;D;D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.42
MVP		0.32
MPC		1.5
ClinPred		0.13	T
GERP RS		2.3
gMVP		0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs115793818; hg19: chr6-32729613;