17-16427514-C-G

Position:

• chr17-16427514-C-G

Variant summary

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

The NM_016113.5(TRPV2):​c.1317C>G​(p.Ile439Met) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPV2 NM_016113.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.297

Genes affected

TRPV2 (HGNC:18082): (transient receptor potential cation channel subfamily V member 2) This gene encodes an ion channel that is activated by high temperatures above 52 degrees Celsius. The protein may be involved in transduction of high-temperature heat responses in sensory ganglia. It is thought that in other tissues the channel may be activated by stimuli other than heat. [provided by RefSeq, Jul 2008]

(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=0.31897283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV2	NM_016113.5	c.1317C>G	p.Ile439Met	missense_variant	8/15	ENST00000338560.12	NP_057197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV2	ENST00000338560.12	c.1317C>G	p.Ile439Met	missense_variant	8/15	1	NM_016113.5	ENSP00000342222	P1
	ENST00000441875.1	n.41C>G		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Ambry Genetics

Oct 13, 2021

The c.1317C>G (p.I439M) alteration is located in exon 8 (coding exon 7) of the TRPV2 gene. This alteration results from a C to G substitution at nucleotide position 1317, causing the isoleucine (I) at amino acid position 439 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	9.4
DANN	Benign	0.56
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.76	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.22
Sift	Benign	0.095	T
Sift4G	Benign	0.16	T
Polyphen		0.13	B
Vest4		0.28
MutPred		0.51		Loss of loop (P = 0.0374);
MVP		0.74
MPC		0.28
ClinPred		0.20	T
GERP RS		2.0
Varity_R		0.062
gMVP		0.45

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: rs201825898; hg19: chr17-16330828;