5-90706236-A-G

Position:

chr5-90706236-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032119.4(ADGRV1):c.8572A>G(p.Ile2858Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,605,208 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:7

Conservation

PhyloP100: 0.882

Variant links:

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010397762).

BP6

Variant 5-90706236-A-G is Benign according to our data. Variant chr5-90706236-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46393.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=1, Uncertain_significance=4}. Variant chr5-90706236-A-G is described in Lovd as [Likely_benign]. Variant chr5-90706236-A-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAdExome4 at 7 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.8572A>G	p.Ile2858Val	missense_variant	38/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.8572A>G	p.Ile2858Val	missense_variant	38/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.000841

AC:

128

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000986

AC:

238

AN:

241322

Hom.:

AF XY:

0.000933

AC XY:

122

AN XY:

130802

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.0000614

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.00219

Gnomad NFE exome

AF:

0.00162

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00191

AC:

2774

AN:

1452906

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1320

AN XY:

722280

show subpopulations

Gnomad4 AFR exome

AF:

0.000334

Gnomad4 AMR exome

AF:

0.0000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00218

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000840

AC:

128

AN:

152302

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000850

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000818

AC:

ESP6500EA

AF:

0.00135

AC:

ExAC

AF:

0.000911

AC:

110

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 12, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 15, 2017	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 15, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 06, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 07, 2016	p.Ile2858Val in exon 38 of GPR98: This variant is not expected to have clinical significance because the isoleucine (Ile) at position 2858 is not conserved thro ugh species with 8 mammals having a valine (Val) at this position. In addition, this variant has been identified in 0.1% (91/65792) of European chromosomes an d in 0.2% (15/6590) of Finnish chromosomes by the Exome Aggregation Consortium ( ExAC, http://exac.broadinstitute.org; dbSNP rs41308297). -

Usher syndrome type 2C

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

ADGRV1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.9

DANN

Benign

0.36

DEOGEN2

Benign

0.048

T;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.66

.;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.92

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.25

.;N;.

REVEL

Benign

0.041

Sift

Benign

0.71

.;T;.

Sift4G

Benign

0.61

.;T;.

Polyphen

0.0050

B;B;.

Vest4

0.23

MVP

0.17

MPC

0.042

ClinPred

0.0017

GERP RS

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.29

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