Variant X-18996092-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001079858.3(ADGRG2):c.2675G>A(p.Arg892Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,186,107 control chromosomes in the GnomAD database, including 5 homozygotes. There are 863 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 40 hem., cov: 23)

Exomes 𝑓: 0.0025 ( 5 hom. 823 hem. )

Consequence

ADGRG2
NM_001079858.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.776

Variant links:

Genes affected

ADGRG2 (HGNC:4516): (adhesion G protein-coupled receptor G2) This gene encodes a member of the G protein-coupled receptor family described as an epididymis-specific transmembrane protein. The encoded protein may be proteolytically processed as it contains a motif shown to be a protein scission motif in some members of this family (PMID: 11973329). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ADGRG2 links:

ENSG00000286724 (HGNC:):

ENSG00000286724 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024146676).

BP6

Variant X-18996092-C-T is Benign according to our data. Variant chrX-18996092-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 40 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG2	NM_001079858.3 linkuse as main transcript	c.2675G>A	p.Arg892Gln	missense_variant	27/29	ENST00000379869.8	NP_001073327.1	Q8IZP9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG2	ENST00000379869.8 linkuse as main transcript	c.2675G>A	p.Arg892Gln	missense_variant	27/29	1	NM_001079858.3	ENSP00000369198.3		Q8IZP9-1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

154

AN:

110954

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

33236

show subpopulations

Gnomad AFR

AF:

0.000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000387

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00255

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00123

AC:

223

AN:

181908

Hom.:

AF XY:

0.00120

AC XY:

AN XY:

66438

show subpopulations

Gnomad AFR exome

AF:

0.000305

Gnomad AMR exome

AF:

0.000815

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000730

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00254

AC:

2733

AN:

1075102

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

823

AN XY:

343500

show subpopulations

Gnomad4 AFR exome

AF:

0.000462

Gnomad4 AMR exome

AF:

0.000914

Gnomad4 ASJ exome

AF:

0.0000521

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.0000564

Gnomad4 FIN exome

AF:

0.000272

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.00139

AC:

154

AN:

111005

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

33297

show subpopulations

Gnomad4 AFR

AF:

0.000327

Gnomad4 AMR

AF:

0.000387

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00255

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00148

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00238

AC:

ExAC

AF:

0.00123

AC:

149

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

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

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D;D;D;.

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.024

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

MetaSVM

Benign

-0.56

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N;N;.;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.027

D;T;T;.;D;D;D;T;D;D

Sift4G

Benign

0.10

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

Polyphen

1.0

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

Vest4

0.24

MVP

0.62

MPC

0.73

ClinPred

0.014

GERP RS

4.7

Varity_R

0.31

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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