Variant rs35288229 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003307.4(TRPM2):c.2263C>T(p.Arg755Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 1,612,656 control chromosomes in the GnomAD database, including 2,430 homozygotes. 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: 𝑓 0.041 ( 188 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2242 hom. )

Consequence

TRPM2
NM_003307.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113

Variant links:

Genes affected

TRPM2 (HGNC:12339): (transient receptor potential cation channel subfamily M member 2) The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]

TRPM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003799945).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM2	NM_003307.4 linkuse as main transcript	c.2263C>T	p.Arg755Cys	missense_variant	15/32	ENST00000397928.6	NP_003298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6 linkuse as main transcript	c.2263C>T	p.Arg755Cys	missense_variant	15/32	1	NM_003307.4	ENSP00000381023	P1	O94759-1

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6198

AN:

152156

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00985

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0579

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0409

AC:

10192

AN:

249314

Hom.:

286

AF XY:

0.0416

AC XY:

5634

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.00824

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0184

Gnomad FIN exome

AF:

0.0928

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0441

GnomAD4 exome

AF:

0.0521

AC:

76037

AN:

1460382

Hom.:

2242

Cov.:

AF XY:

0.0515

AC XY:

37409

AN XY:

726484

show subpopulations

Gnomad4 AFR exome

AF:

0.00759

Gnomad4 AMR exome

AF:

0.0234

Gnomad4 ASJ exome

AF:

0.0299

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0196

Gnomad4 FIN exome

AF:

0.0941

Gnomad4 NFE exome

AF:

0.0582

Gnomad4 OTH exome

AF:

0.0417

GnomAD4 genome

AF:

0.0407

AC:

6198

AN:

152274

Hom.:

188

Cov.:

AF XY:

0.0409

AC XY:

3043

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00982

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.0326

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0579

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0494

Hom.:

147

Bravo

AF:

0.0331

TwinsUK

AF:

0.0545

AC:

202

ALSPAC

AF:

0.0631

AC:

243

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.0548

AC:

471

ExAC

AF:

0.0404

AC:

4898

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0522

EpiControl

AF:

0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;D;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.95

.;D;D;D

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Pathogenic

3.1

M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.8

D;D;D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.68

MPC

0.69

ClinPred

0.055

GERP RS

1.7

Varity_R

0.63

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over