17-16422739-G-A

Variant names:

• chr17-16422739-G-A
• rs368460322
• NM_016113.5:c.475G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016113.5(TRPV2):​c.475G>A​(p.Asp159Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,591,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: TRPV2 NM_016113.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09027377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016113.5. 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
	TRPV2	NM_016113.5	MANE Select	c.475G>A	p.Asp159Asn	missense	Exon 4 of 15	NP_057197.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV2	ENST00000338560.12	TSL:1 MANE Select	c.475G>A	p.Asp159Asn	missense	Exon 4 of 15	ENSP00000342222.7	Q9Y5S1
	TRPV2	ENST00000455666.1	TSL:3	c.346G>A	p.Asp116Asn	missense	Exon 3 of 4	ENSP00000390014.1	H7BZK2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152250 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000906 AC: 19 AN: 209802 AF XY: 0.0000885

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.000185

GnomAD4 exome AF: 0.000151 AC: 218 AN: 1439338 Hom.: 0 Cov.: 36 AF XY: 0.000140 AC XY: 100 AN XY: 714168

African (AFR) AF: 0.00 AC: 0 AN: 32848

American (AMR) AF: 0.0000242 AC: 1 AN: 41306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 38474

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83486

European-Finnish (FIN) AF: 0.0000765 AC: 4 AN: 52260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000186 AC: 205 AN: 1100014

Other (OTH) AF: 0.000118 AC: 7 AN: 59544

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152250 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74380

African (AFR) AF: 0.0000482 AC: 2 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68044

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000826 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.42	N
PhyloP100		2.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.096
Sift	Benign	0.45	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.12
MVP		0.81
MPC		0.34
ClinPred		0.031	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.35
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs368460322; hg19: chr17-16326053; COSMIC: COSV105911156; COSMIC: COSV105911156;