rs2366926

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000405460.9(ADGRV1):c.7034A>G(p.Asn2345Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,608,380 control chromosomes in the GnomAD database, including 97,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2345I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.32 ( 8066 hom., cov: 32)

Exomes 𝑓: 0.35 ( 89209 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 9.06

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027406216).

BP6

Variant 5-90692687-A-G is Benign according to our data. Variant chr5-90692687-A-G is described in ClinVar as [Benign]. Clinvar id is 46360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90692687-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.7034A>G	p.Asn2345Ser	missense_variant	32/90	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.7034A>G	p.Asn2345Ser	missense_variant	32/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47895

AN:

151834

Hom.:

8053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.358

AC:

86812

AN:

242400

Hom.:

16833

AF XY:

0.351

AC XY:

46018

AN XY:

131272

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.580

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.369

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.345

AC:

502654

AN:

1456428

Hom.:

89209

Cov.:

AF XY:

0.343

AC XY:

248130

AN XY:

724100

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.315

AC:

47914

AN:

151952

Hom.:

8066

Cov.:

AF XY:

0.318

AC XY:

23645

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.335

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.335

Hom.:

21793

Bravo

AF:

0.327

TwinsUK

AF:

0.331

AC:

1229

ALSPAC

AF:

0.349

AC:

1346

ESP6500AA

AF:

0.208

AC:

777

ESP6500EA

AF:

0.329

AC:

2701

ExAC

AF:

0.345

AC:

41612

Asia WGS

AF:

0.343

AC:

1195

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 16, 2007	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Usher syndrome type 2C

Benign:1

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;D

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

7.4e-8

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.0

.;D;.

REVEL

Uncertain

0.41

Sift

Benign

0.12

.;T;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.29

MPC

0.26

ClinPred

0.018

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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