NM_032119.4:c.8300C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032119.4(ADGRV1):c.8300C>T(p.Thr2767Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.74

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108299434).

BP6

Variant 5-90704402-C-T is Benign according to our data. Variant chr5-90704402-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 506021.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.8300C>T	p.Thr2767Ile	missense_variant	Exon 36 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.8300C>T	p.Thr2767Ile	missense_variant	Exon 36 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1420320

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32680

American (AMR)

AF:

0.00

AC:

AN:

39542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25454

East Asian (EAS)

AF:

0.00

AC:

AN:

38162

South Asian (SAS)

AF:

0.0000125

AC:

AN:

79688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088704

Other (OTH)

AF:

0.00

AC:

AN:

59004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 25, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Thr2767Ile in exon 36 of GPR98: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, 4 mammals (sheep, domestic goat, bat and big brown bat) have an isoleucin e (Ile) at this position despite high nearby amino acid conservation. In additio n, computational prediction tools do not suggest a high likelihood of impact to the protein. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.57

.;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

1.7

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.2

.;N;.

REVEL

Benign

0.063

Sift

Benign

0.17

.;T;.

Sift4G

Benign

0.15

.;T;.

Polyphen

0.081

B;B;.

Vest4

0.15

MutPred

0.49

Loss of glycosylation at T2767 (P = 0.0618);Loss of glycosylation at T2767 (P = 0.0618);.;

MVP

0.30

MPC

0.052

ClinPred

0.15

GERP RS

3.7

Varity_R

0.087

gMVP

0.39

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over