dbSNP rs149701008: ADGRB2:p.Glu1572Asp (chr1-31727462-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001364857.2(ADGRB2):c.4716G>T(p.Glu1572Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E1572E) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRB2
NM_001364857.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.185

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15503657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRB2	NM_001364857.2	MANE Select	c.4716G>T	p.Glu1572Asp	missense	Exon 33 of 33	NP_001351786.1	O60241-1
ADGRB2	NM_001294335.2		c.4713G>T	p.Glu1571Asp	missense	Exon 33 of 33	NP_001281264.1	O60241-2
ADGRB2	NM_001294336.2		c.4614G>T	p.Glu1538Asp	missense	Exon 32 of 32	NP_001281265.1	O60241-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRB2	ENST00000373658.8	TSL:5 MANE Select	c.4716G>T	p.Glu1572Asp	missense	Exon 33 of 33	ENSP00000362762.3	O60241-1
ADGRB2	ENST00000373655.6	TSL:1	c.4713G>T	p.Glu1571Asp	missense	Exon 33 of 33	ENSP00000362759.2	O60241-2
ADGRB2	ENST00000527361.5	TSL:1	c.4614G>T	p.Glu1538Asp	missense	Exon 30 of 30	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000884

AC:

AN:

226298

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1438564

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31646

American (AMR)

AF:

0.00

AC:

AN:

36724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25046

East Asian (EAS)

AF:

0.00

AC:

AN:

38734

South Asian (SAS)

AF:

0.00

AC:

AN:

82556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105594

Other (OTH)

AF:

0.00

AC:

AN:

59334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

PhyloP100

0.18

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.1

REVEL

Benign

0.034

Sift

Pathogenic

0.0

Sift4G

Benign

0.066

Polyphen

0.96

Vest4

0.16

MutPred

0.26

Loss of catalytic residue at E1572 (P = 0.0055)

MVP

0.31

MPC

0.83

ClinPred

0.83

GERP RS

3.1

Varity_R

0.40

gMVP

0.19

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over