Genetic Variant NM_016113.5:c.505A>G (chr17-16422769-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016113.5(TRPV2):c.505A>G(p.Ile169Val) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,575,176 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

TRPV2
NM_016113.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

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]

TRPV2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041771412).

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.505A>G	p.Ile169Val	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.505A>G	p.Ile169Val	missense	Exon 4 of 15	ENSP00000342222.7	Q9Y5S1
	TRPV2	ENST00000455666.1	TSL:3	c.376A>G	p.Ile126Val	missense	Exon 3 of 4	ENSP00000390014.1	H7BZK2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000236

AC:

AN:

186720

AF XY:

0.000171

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000535

Gnomad ASJ exome

AF:

0.00267

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000387

Gnomad OTH exome

AF:

0.000402

GnomAD4 exome

AF:

0.000101

AC:

143

AN:

1422800

Hom.:

Cov.:

AF XY:

0.0000980

AC XY:

AN XY:

704306

show subpopulations

African (AFR)

AF:

0.000154

AC:

AN:

32458

American (AMR)

AF:

0.000792

AC:

AN:

39120

Ashkenazi Jewish (ASJ)

AF:

0.00271

AC:

AN:

25424

East Asian (EAS)

AF:

0.00

AC:

AN:

37490

South Asian (SAS)

AF:

0.00

AC:

AN:

81748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51148

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000174

AC:

AN:

1090790

Other (OTH)

AF:

0.000272

AC:

AN:

58888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000203

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41588

American (AMR)

AF:

0.000915

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68042

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000275

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000183

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.035

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.43

MutationAssessor

Benign

0.76

PhyloP100

4.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.70

REVEL

Benign

0.26

Sift

Benign

0.088

Sift4G

Benign

0.16

Polyphen

0.89

Vest4

0.41

MVP

0.77

MPC

0.82

ClinPred

0.12

GERP RS

5.9

Varity_R

0.18

gMVP

0.65

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over