rs2366926

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032119.4(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
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.06

Publications

40 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 -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 VariationId is 46360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.7034A>G	p.Asn2345Ser	missense_variant	Exon 32 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.7034A>G	p.Asn2345Ser	missense_variant	Exon 32 of 90	1	NM_032119.4	ENSP00000384582.2		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

GnomAD2 exomes

AF:

0.358

AC:

86812

AN:

242400

AF XY:

0.351

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 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

African (AFR)

AF:

0.205

AC:

6842

AN:

33410

American (AMR)

AF:

0.567

AC:

24940

AN:

43956

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

7078

AN:

26050

East Asian (EAS)

AF:

0.433

AC:

17128

AN:

39550

South Asian (SAS)

AF:

0.327

AC:

27938

AN:

85396

European-Finnish (FIN)

AF:

0.340

AC:

18098

AN:

53202

Middle Eastern (MID)

AF:

0.274

AC:

1578

AN:

5764

European-Non Finnish (NFE)

AF:

0.342

AC:

378824

AN:

1108934

Other (OTH)

AF:

0.336

AC:

20228

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

15590

31180

46771

62361

77951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12316

24632

36948

49264

61580

<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:

0.315

AC:

47914

AN:

151952

Hom.:

8066

Cov.:

AF XY:

0.318

AC XY:

23645

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.215

AC:

8927

AN:

41446

American (AMR)

AF:

0.472

AC:

7200

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

958

AN:

3470

East Asian (EAS)

AF:

0.386

AC:

1994

AN:

5170

South Asian (SAS)

AF:

0.320

AC:

1542

AN:

4816

European-Finnish (FIN)

AF:

0.335

AC:

3535

AN:

10554

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.333

AC:

22631

AN:

67936

Other (OTH)

AF:

0.345

AC:

723

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1644

3289

4933

6578

8222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.334

Hom.:

41102

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

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 16, 2007

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

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

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

PhyloP100

9.1

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

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

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