Variant chr21-44366787-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003307.4(TRPM2):c.457G>A(p.Val153Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,613,816 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0047 ( 25 hom. )

Consequence

TRPM2
NM_003307.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.128

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006235808).

BP6

Variant 21-44366787-G-A is Benign according to our data. Variant chr21-44366787-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM2	NM_003307.4 linkuse as main transcript	c.457G>A	p.Val153Met	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.457G>A	p.Val153Met	missense_variant	4/32	1	NM_003307.4	P1	O94759-1

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

530

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00227

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00653

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00328

AC:

825

AN:

251324

Hom.:

AF XY:

0.00321

AC XY:

436

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00574

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00466

AC:

6813

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

3324

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.000803

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.00564

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00349

AC:

530

AN:

151990

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00227

Gnomad4 NFE

AF:

0.00653

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00528

Hom.:

Bravo

AF:

0.00321

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00340

AC:

413

EpiCase

AF:

0.00480

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.27

T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.48

.;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;L;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.93

P;P;D;.

Vest4

0.23

MVP

0.12

MPC

0.16

ClinPred

0.0057

GERP RS

-1.4

Varity_R

0.071

gMVP

0.23

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