Variant 21-44424718-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003307.4(TRPM2):c.3550-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 546,016 control chromosomes in the GnomAD database, including 110,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 25456 hom., cov: 30)

Exomes 𝑓: 0.65 ( 85393 hom. )

Consequence

TRPM2
NM_003307.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.75

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:

TRPM2-AS (HGNC:50758): (TRPM2 antisense RNA)

TRPM2-AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 21-44424718-C-T is Benign according to our data. Variant chr21-44424718-C-T is described in ClinVar as [Benign]. Clinvar id is 1242396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM2	NM_003307.4 link	c.3550-134C>T		intron_variant		ENST00000397928.6	NP_003298.2	O94759-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6 link	c.3550-134C>T		intron_variant		1	NM_003307.4	ENSP00000381023.1		O94759-1

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81577

AN:

151446

Hom.:

25461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.694

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.529

Gnomad NFE

AF:

0.691

Gnomad OTH

AF:

0.571

GnomAD4 exome

AF:

0.651

AC:

256677

AN:

394450

Hom.:

85393

AF XY:

0.649

AC XY:

132098

AN XY:

203664

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.581

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.685

Gnomad4 NFE exome

AF:

0.687

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.538

AC:

81575

AN:

151566

Hom.:

25456

Cov.:

AF XY:

0.540

AC XY:

39988

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.195

Gnomad4 AMR

AF:

0.604

Gnomad4 ASJ

AF:

0.629

Gnomad4 EAS

AF:

0.693

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.684

Gnomad4 NFE

AF:

0.691

Gnomad4 OTH

AF:

0.571

Alfa

AF:

0.631

Hom.:

5959

Bravo

AF:

0.518

Asia WGS

AF:

0.546

AC:

1899

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.8

DANN

Benign

0.71

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