Variant chr21-44417907-T-C 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.3147-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,602,140 control chromosomes in the GnomAD database, including 447,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38164 hom., cov: 33)

Exomes 𝑓: 0.75 ( 409038 hom. )

Consequence

TRPM2
NM_003307.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.507

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 21-44417907-T-C is Benign according to our data. Variant chr21-44417907-T-C is described in ClinVar as [Benign]. Clinvar id is 1261780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM2	NM_003307.4 link	c.3147-20T>C		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.3147-20T>C		intron_variant		1	NM_003307.4	ENSP00000381023.1		O94759-1

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106573

AN:

151930

Hom.:

38154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.770

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.722

GnomAD3 exomes

AF:

0.737

AC:

179779

AN:

243952

Hom.:

66860

AF XY:

0.736

AC XY:

97647

AN XY:

132598

show subpopulations

Gnomad AFR exome

AF:

0.542

Gnomad AMR exome

AF:

0.776

Gnomad ASJ exome

AF:

0.719

Gnomad EAS exome

AF:

0.802

Gnomad SAS exome

AF:

0.667

Gnomad FIN exome

AF:

0.757

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.748

GnomAD4 exome

AF:

0.750

AC:

1087032

AN:

1450092

Hom.:

409038

Cov.:

AF XY:

0.748

AC XY:

538627

AN XY:

720350

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.777

Gnomad4 ASJ exome

AF:

0.719

Gnomad4 EAS exome

AF:

0.769

Gnomad4 SAS exome

AF:

0.670

Gnomad4 FIN exome

AF:

0.758

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.740

GnomAD4 genome

AF:

0.701

AC:

106631

AN:

152048

Hom.:

38164

Cov.:

AF XY:

0.701

AC XY:

52108

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.547

Gnomad4 AMR

AF:

0.770

Gnomad4 ASJ

AF:

0.715

Gnomad4 EAS

AF:

0.782

Gnomad4 SAS

AF:

0.666

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.721

Alfa

AF:

0.735

Hom.:

9952

Bravo

AF:

0.696

Asia WGS

AF:

0.687

AC:

2383

AN:

3468

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

1.2

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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