Variant 21-44401911-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 ENST00000397928.6(TRPM2):c.2538+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,612,988 control chromosomes in the GnomAD database, including 455,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41860 hom., cov: 32)

Exomes 𝑓: 0.75 ( 413289 hom. )

Consequence

TRPM2
ENST00000397928.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.07

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 21-44401911-C-T is Benign according to our data. Variant chr21-44401911-C-T is described in ClinVar as [Benign]. Clinvar id is 1251349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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.2538+14C>T		intron_variant		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.2538+14C>T		intron_variant		1	NM_003307.4	ENSP00000381023	P1	O94759-1

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112593

AN:

151836

Hom.:

41845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.750

GnomAD3 exomes

AF:

0.737

AC:

184596

AN:

250366

Hom.:

68349

AF XY:

0.735

AC XY:

99634

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.723

Gnomad EAS exome

AF:

0.792

Gnomad SAS exome

AF:

0.652

Gnomad FIN exome

AF:

0.753

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.746

GnomAD4 exome

AF:

0.751

AC:

1097706

AN:

1461034

Hom.:

413289

Cov.:

AF XY:

0.749

AC XY:

544242

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.700

Gnomad4 AMR exome

AF:

0.729

Gnomad4 ASJ exome

AF:

0.722

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.754

Gnomad4 NFE exome

AF:

0.762

Gnomad4 OTH exome

AF:

0.745

GnomAD4 genome

AF:

0.741

AC:

112662

AN:

151954

Hom.:

41860

Cov.:

AF XY:

0.739

AC XY:

54880

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.652

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.767

Gnomad4 OTH

AF:

0.749

Alfa

AF:

0.756

Hom.:

8303

Bravo

AF:

0.741

Asia WGS

AF:

0.687

AC:

2389

AN:

3476

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

-0.97

CADD

Benign

0.032

DANN

Benign

0.72

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