rs3813768

Positions:

• chr17-16417718-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000338560.12(TRPV2):​c.50G>C​(p.Gly17Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00863 in 1,614,164 control chromosomes in the GnomAD database, including 1,066 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0097 (125 hom., cov: 31)
  • Exomes 𝑓: 0.0085 (941 hom.)
• Consequence: TRPV2 ENST00000338560.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012409985).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV2	NM_016113.5	c.50G>C	p.Gly17Ala	missense_variant	2/15	ENST00000338560.12	NP_057197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV2	ENST00000338560.12	c.50G>C	p.Gly17Ala	missense_variant	2/15	1	NM_016113.5	ENSP00000342222	P1

Frequencies

GnomAD3 genomes AF: 0.00973 AC: 1481 AN: 152162 Hom.: 125 Cov.: 31

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.0206 AC: 5169 AN: 251468 Hom.: 441 AF XY: 0.0195 AC XY: 2656 AN XY: 135916

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.00387

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.0178

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.00994

GnomAD4 exome AF: 0.00852 AC: 12449 AN: 1461884 Hom.: 941 Cov.: 31 AF XY: 0.00867 AC XY: 6304 AN XY: 727244

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.00444

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.00970 AC: 1477 AN: 152280 Hom.: 125 Cov.: 31 AF XY: 0.0110 AC XY: 816 AN XY: 74446

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00948

Alfa AF: 0.00291 Hom.: 2

Bravo AF: 0.0111

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.00233 AC: 20

ExAC AF: 0.0200 AC: 2423

Asia WGS AF: 0.0850 AC: 294 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.000771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.20
Sift	Benign	0.12	T
Sift4G	Benign	0.48	T
Polyphen		0.0040	B
Vest4		0.12
MPC		0.32
ClinPred		0.0030	T
GERP RS		3.5
Varity_R		0.052
gMVP		0.17

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: rs3813768; hg19: chr17-16321032; COSMIC: COSV58427728; COSMIC: COSV58427728;