chr5-90694507-A-T

Position:

• chr5-90694507-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032119.4(ADGRV1):​c.7751A>T​(p.Asn2584Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2584S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.65

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2727902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.7751A>T	p.Asn2584Ile	missense_variant	33/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.7751A>T	p.Asn2584Ile	missense_variant	33/90	1	NM_032119.4	ENSP00000384582	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	.;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.81	P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	.;N;.
REVEL	Benign	0.21
Sift	Uncertain	0.0020	.;D;.
Sift4G	Pathogenic	0.0010	.;D;.
Polyphen		0.023	B;B;.
Vest4		0.29
MutPred		0.46		Loss of catalytic residue at N2584 (P = 0.034);Loss of catalytic residue at N2584 (P = 0.034);.;
MVP		0.42
MPC		0.059
ClinPred		0.77	D
GERP RS		5.9
Varity_R		0.40
gMVP		0.60

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

Other links and lift over

dbSNP: rs1878878; hg19: chr5-89990324;