rs41302834

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000405460.9(ADGRV1):c.5830G>A(p.Asp1944Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,613,812 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1944Y) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 34 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 9.87

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=0.00907135).

BP6

Variant 5-90683751-G-A is Benign according to our data. Variant chr5-90683751-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90683751-G-A is described in Lovd as [Benign]. Variant chr5-90683751-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00605 (8840/1461642) while in subpopulation NFE AF= 0.00681 (7569/1111838). AF 95% confidence interval is 0.00668. There are 34 homozygotes in gnomad4_exome. There are 4292 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.5830G>A	p.Asp1944Asn	missense_variant	28/90	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.5830G>A	p.Asp1944Asn	missense_variant	28/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

655

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00669

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00589

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00433

AC:

1077

AN:

248838

Hom.:

AF XY:

0.00425

AC XY:

574

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.00200

Gnomad NFE exome

AF:

0.00578

Gnomad OTH exome

AF:

0.00464

GnomAD4 exome

AF:

0.00605

AC:

8840

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

4292

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.00245

Gnomad4 NFE exome

AF:

0.00681

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00430

AC:

655

AN:

152170

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00668

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00590

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00614

Hom.:

Bravo

AF:

0.00415

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00724

AC:

ExAC

AF:

0.00400

AC:

483

EpiCase

AF:

0.00643

EpiControl

AF:

0.00652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ADGRV1: BS2 -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 05, 2022	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 21, 2018	This variant is associated with the following publications: (PMID: 25262649, 21569298, 30245029, 32707200) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 25, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 07, 2016	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 10, 2012	Asp1944Asn in exon 28 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (50/6688) of European American chromosomes in a broad population by the NHLBI Exome sequencing project (http:/ /evs.gs.washington.edu/EVS/; dbSNP rs41302834). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 27, 2014	- -

Usher syndrome type 2C

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;T;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0091

T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.2

.;D;.

REVEL

Benign

0.29

Sift

Uncertain

0.026

.;D;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.75

MVP

0.75

MPC

0.31

ClinPred

0.019

GERP RS

5.7

Varity_R

0.50

gMVP

0.74

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