Variant chr1-31727493-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001364857.2(ADGRB2):c.4685G>A(p.Arg1562Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,444,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADGRB2
NM_001364857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

ADGRB2 (HGNC:944): (adhesion G protein-coupled receptor B2) This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ADGRB2 links:

ADGRB2 (HGNC:):

ADGRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.104243845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRB2	NM_001364857.2 linkuse as main transcript	c.4685G>A	p.Arg1562Gln	missense_variant	33/33	ENST00000373658.8	NP_001351786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRB2	ENST00000373658.8 linkuse as main transcript	c.4685G>A	p.Arg1562Gln	missense_variant	33/33	5	NM_001364857.2	ENSP00000362762.3		O60241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000430

AC:

AN:

232478

Hom.:

AF XY:

0.00000790

AC XY:

AN XY:

126616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1444554

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

718922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000773

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 23, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ADGRB2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 1528 of the ADGRB2 protein (p.Arg1528Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;.;T;T;.;T

Eigen

Benign

0.029

Eigen_PC

Benign

0.087

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.68

N;N;N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.20

T;T;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;T;T

Polyphen

0.97, 0.82, 0.93

.;.;D;.;P;D;P

Vest4

0.21

MutPred

0.22

.;.;.;.;Gain of methylation at K1558 (P = 0.0672);.;.;

MVP

0.082

MPC

1.1

ClinPred

0.40

GERP RS

4.2

Varity_R

0.088

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over