Genetic Variant NM_016113.5:c.427A>T (chr17-16422691-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016113.5(TRPV2):c.427A>T(p.Arg143Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TRPV2
NM_016113.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.783

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2977643).

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.427A>T	p.Arg143Trp	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.427A>T	p.Arg143Trp	missense	Exon 4 of 15	ENSP00000342222.7
	TRPV2	ENST00000455666.1	TSL:3	c.298A>T	p.Arg100Trp	missense	Exon 3 of 4	ENSP00000390014.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245518

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458888

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

85798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1110390

Other (OTH)

AF:

0.0000166

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.30

MetaSVM

Uncertain

-0.052

MutationAssessor

Benign

1.3

PhyloP100

-0.78

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.94

Vest4

0.26

MutPred

0.49

Loss of disorder (P = 0.0206)

MVP

0.81

MPC

0.46

ClinPred

0.93

GERP RS

-2.9

Varity_R

0.44

gMVP

0.54

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over