NM_032119.4:c.6133G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.6133G>A(p.Gly2045Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,613,882 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 48 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:14

Conservation

PhyloP100: 9.69

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
febrile seizures, familial, 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: BayesDel_noAF, Dann, Eigen, FATHMM_MKL, M_CAP, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.011430383).

BP6

Variant 5-90684054-G-A is Benign according to our data. Variant chr5-90684054-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00461 (702/152222) while in subpopulation NFE AF = 0.00816 (555/68000). AF 95% confidence interval is 0.0076. There are 2 homozygotes in GnomAd4. There are 325 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.6133G>A	p.Gly2045Arg	missense_variant	Exon 28 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.6133G>A	p.Gly2045Arg	missense_variant	Exon 28 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00462

AC:

702

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00426

AC:

1058

AN:

248490

AF XY:

0.00425

show subpopulations

Gnomad AFR exome

AF:

0.000775

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00448

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00362

Gnomad NFE exome

AF:

0.00725

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00646

AC:

9441

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

4585

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33478

American (AMR)

AF:

0.00197

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00413

AC:

108

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000684

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00451

AC:

241

AN:

53396

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00772

AC:

8588

AN:

1111850

Other (OTH)

AF:

0.00533

AC:

322

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

545

1091

1636

2182

2727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00461

AC:

702

AN:

152222

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

325

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41548

American (AMR)

AF:

0.00275

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00415

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00816

AC:

555

AN:

68000

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00696

Hom.:

Bravo

AF:

0.00430

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000273

AC:

ESP6500EA

AF:

0.00797

AC:

ExAC

AF:

0.00439

AC:

530

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00634

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:8

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 31, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 25, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24498627, 30245029, 32707200) -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ADGRV1: BS2 -

Mar 29, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 12, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 14, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Gly2045Arg in exon 28 of GPR98: This variant is not expected to have clinical significance because it has been identified in 0.7% (480/67628) of European chro mosomes by the Exome Aggregation Consortium, including one homozygote (ExAC, htt p://exac.broadinstitute.org; dbSNP rs41308846). -

Jan 02, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:2

Apr 08, 2025

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Febrile seizures, familial, 4

Uncertain:1

Mar 03, 2014

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:flagged submission

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

T;T;.

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

.;T;T

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.34

PhyloP100

9.7

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.4

.;D;.

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0030

.;D;.

Sift4G

Uncertain

0.0050

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.90

MutPred

0.79

Loss of glycosylation at S2044 (P = 0.0283);Loss of glycosylation at S2044 (P = 0.0283);.;

MVP

0.75

MPC

0.35

ClinPred

0.034

GERP RS

5.7

Varity_R

0.74

gMVP

0.76

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over