Genetic Variant ADGRV1:p.Asp4707Tyr (chr5-90790948-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_032119.4(ADGRV1):c.14119G>T(p.Asp4707Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,570 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D4707V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.44

Publications

2 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: Uncertain_significance. The variant received 1 ACMG points.

PP5

Variant 5-90790948-G-T is Pathogenic according to our data. Variant chr5-90790948-G-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 226443.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.14119G>T	p.Asp4707Tyr	missense_variant	Exon 70 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.14119G>T	p.Asp4707Tyr	missense_variant	Exon 70 of 90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460570

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.000614

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111822

Other (OTH)

AF:

0.00

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Usher syndrome type 1

Pathogenic:1

May 19, 2016

GeneReviews

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;.;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Benign

-0.79

PhyloP100

4.4

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.3

.;D;.;.

REVEL

Benign

0.21

Sift

Uncertain

0.0020

.;D;.;.

Sift4G

Uncertain

0.0050

.;D;.;.

Polyphen

1.0

D;D;.;.

Vest4

0.72

MutPred

0.47

Loss of disorder (P = 0.0161);Loss of disorder (P = 0.0161);.;.;

MVP

0.68

MPC

0.35

ClinPred

0.97

GERP RS

4.8

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.69

gMVP

0.64

Mutation Taster

=23/77

disease causing (ClinVar)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over