5-90675436-G-T

Variant names:

• chr5-90675436-G-T
• rs41303346
• NM_032119.4:c.5304G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032119.4(ADGRV1):​c.5304G>T​(p.Glu1768Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. E1768K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 2 publications found

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: Orphanet, ClinGen
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17862356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.5304G>T	p.Glu1768Asp	missense	Exon 24 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.5403G>T		non_coding_transcript_exon	Exon 24 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5304G>T	p.Glu1768Asp	missense	Exon 24 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000450321.2	TSL:1	n.*422G>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000492054.1	A0A1W2PR51
	ADGRV1	ENST00000450321.2	TSL:1	n.*422G>T		3_prime_UTR	Exon 4 of 6	ENSP00000492054.1	A0A1W2PR51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.37
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.015
Sift	Benign	0.45	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.15
MutPred		0.29		Loss of loop (P = 0.1242)
MVP		0.26
MPC		0.067
ClinPred		0.16	T
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.34
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs41303346; hg19: chr5-89971253;