NM_032119.4:c.6695A>G

Variant names:

Variant summary

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

The NM_032119.4(ADGRV1):c.6695A>G(p.Tyr2232Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,545,226 control chromosomes in the GnomAD database, including 94,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9004 hom., cov: 31)

Exomes 𝑓: 0.34 ( 85101 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.16

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=5.3060055E-4).

BP6

Variant 5-90690065-A-G is Benign according to our data. Variant chr5-90690065-A-G is described in ClinVar as [Benign]. Clinvar id is 46356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90690065-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.6695A>G	p.Tyr2232Cys	missense_variant	Exon 30 of 90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.6695A>G	p.Tyr2232Cys	missense_variant	Exon 30 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51372

AN:

151848

Hom.:

8980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.365

AC:

66647

AN:

182748

Hom.:

13069

AF XY:

0.356

AC XY:

34582

AN XY:

97230

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.574

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.365

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.345

AC:

480345

AN:

1393260

Hom.:

85101

Cov.:

AF XY:

0.343

AC XY:

236610

AN XY:

690630

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.560

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.340

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.338

AC:

51426

AN:

151966

Hom.:

9004

Cov.:

AF XY:

0.341

AC XY:

25321

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.341

Hom.:

17987

Bravo

AF:

0.353

TwinsUK

AF:

0.333

AC:

1233

ALSPAC

AF:

0.351

AC:

1351

ESP6500AA

AF:

0.293

AC:

1070

ESP6500EA

AF:

0.329

AC:

2688

ExAC

AF:

0.309

AC:

35600

Asia WGS

AF:

0.351

AC:

1221

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

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 23, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2C

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

.;D;D

MetaRNN

Benign

0.00053

T;T;T

MetaSVM

Benign

-0.91

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.3

.;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0070

.;D;.

Sift4G

Uncertain

0.0020

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.24

MPC

0.33

ClinPred

0.027

GERP RS

2.8

Varity_R

0.38

gMVP

0.73

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