Variant 21-44366826-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003307.4(TRPM2):c.496G>A(p.Val166Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,613,640 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.031 ( 236 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 227 hom. )

Consequence

TRPM2
NM_003307.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00900

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003167659).

BP6

Variant 21-44366826-G-A is Benign according to our data. Variant chr21-44366826-G-A is described in ClinVar as [Benign]. Clinvar id is 777642.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM2	NM_003307.4 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	4/32	ENST00000397928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM2	ENST00000397928.6 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	4/32	1	NM_003307.4	P1	O94759-1
TRPM2	ENST00000397932.6 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	4/33	1
TRPM2	ENST00000300482.9 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	5/33	1		P1	O94759-1
TRPM2	ENST00000300481.13 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	4/32	1			O94759-2

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4723

AN:

151788

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0197

GnomAD3 exomes

AF:

0.00796

AC:

1998

AN:

250858

Hom.:

107

AF XY:

0.00597

AC XY:

809

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.00351

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00142

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00315

AC:

4607

AN:

1461734

Hom.:

227

Cov.:

AF XY:

0.00278

AC XY:

2021

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.00647

GnomAD4 genome

AF:

0.0312

AC:

4733

AN:

151906

Hom.:

236

Cov.:

AF XY:

0.0296

AC XY:

2196

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0195

Alfa

AF:

0.00545

Hom.:

Bravo

AF:

0.0353

ESP6500AA

AF:

0.103

AC:

454

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00967

AC:

1174

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.0

DANN

Benign

0.96

DEOGEN2

Benign

0.25

T;T;.;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.069

MetaRNN

Benign

0.0032

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.88

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.45

T;T;T;T

Sift4G

Benign

0.45

T;T;T;T

Polyphen

0.039

B;B;B;.

Vest4

0.16

MVP

0.23

MPC

0.11

ClinPred

0.00063

GERP RS

2.3

Varity_R

0.063

gMVP

0.097

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over