Genetic Variant ADGRB2:p.Arg1540His (chr1-31727559-C-T) – 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.4619G>A(p.Arg1540His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000983 in 1,424,198 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: 0.0000098 ( 0 hom. )

Consequence

ADGRB2
NM_001364857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.761

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=0.12686884).

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.4619G>A	p.Arg1540His	missense	Exon 33 of 33	NP_001351786.1	O60241-1
ADGRB2	NM_001294335.2		c.4616G>A	p.Arg1539His	missense	Exon 33 of 33	NP_001281264.1	O60241-2
ADGRB2	NM_001294336.2		c.4517G>A	p.Arg1506His	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.4619G>A	p.Arg1540His	missense	Exon 33 of 33	ENSP00000362762.3	O60241-1
ADGRB2	ENST00000373655.6	TSL:1	c.4616G>A	p.Arg1539His	missense	Exon 33 of 33	ENSP00000362759.2	O60241-2
ADGRB2	ENST00000527361.5	TSL:1	c.4517G>A	p.Arg1506His	missense	Exon 30 of 30	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000286

AC:

AN:

209702

AF XY:

0.0000349

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000834

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000999

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.00000983

AC:

AN:

1424198

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

707940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30902

American (AMR)

AF:

0.0000582

AC:

AN:

34374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24320

East Asian (EAS)

AF:

0.00

AC:

AN:

37954

South Asian (SAS)

AF:

0.0000624

AC:

AN:

80092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5546

European-Non Finnish (NFE)

AF:

0.00000546

AC:

AN:

1099612

Other (OTH)

AF:

0.0000171

AC:

AN:

58626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0075

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

PhyloP100

0.76

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.94

REVEL

Benign

0.060

Sift

Benign

0.084

Sift4G

Benign

0.071

Polyphen

1.0

Vest4

0.17

MutPred

0.19

Loss of MoRF binding (P = 0.0385)

MVP

0.21

MPC

0.84

ClinPred

0.31

GERP RS

4.3

Varity_R

0.071

gMVP

0.17

Mutation Taster

=83/17

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