rs1554088550

chr5-90704402-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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. 14/20 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74

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 Likely_benign. Variant got -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 id is 506021.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4	c.8300C>T	p.Thr2767Ile	missense_variant	36/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9	c.8300C>T	p.Thr2767Ile	missense_variant	36/90	1	NM_032119.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420320 Hom.: 0 Cov.: 28 AF XY: 0.00000142 AC XY: 1 AN XY: 702502

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 25, 2017

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	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	11
Dann	Benign	0.92
DEOGEN2	Benign	0.12	T;T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.64	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.28	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	T
GERP RS		3.7
Varity_R		0.087
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs1554088550; hg19: chr5-90000219;