rs397517425

Positions:

• chr5-90629411-A-G

Variant summary

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

The NM_032119.4(ADGRV1):​c.1711A>G​(p.Lys571Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

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 (HGNC:):

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=0.3252377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.1711A>G	p.Lys571Glu	missense_variant	9/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.1711A>G	p.Lys571Glu	missense_variant	9/90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000504142.2	n.477A>G		non_coding_transcript_exon_variant	3/14	5
ADGRV1	ENST00000640109.1	n.1807A>G		non_coding_transcript_exon_variant	9/9	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 06, 2013

The Lys571Glu variant in GPR98 has not been described in the literature nor prev iously reported by our laboratory. It has also not been identified in large Euro pean American and African American populations sequenced by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS/). Computational analyses (bioc hemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional information is needed to fully assess the clinical significance of th e Lys571Glu variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.53	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.18
Sift	Benign	0.15	.;T
Sift4G	Uncertain	0.0090	.;D
Polyphen		0.99	D;D
Vest4		0.45
MutPred		0.43		Loss of ubiquitination at K571 (P = 0.0127);Loss of ubiquitination at K571 (P = 0.0127);
MVP		0.53
MPC		0.23
ClinPred		0.91	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs397517425; hg19: chr5-89925228;