dbSNP rs1618355: TRPM2:c.2791-15C>A (chr21-44406579-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_003307.4(TRPM2):c.2791-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,602,260 control chromosomes in the GnomAD database, including 445,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38674 hom., cov: 32)

Exomes 𝑓: 0.75 ( 407026 hom. )

Consequence

TRPM2
NM_003307.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.150

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=-0.83).

BP6

Variant 21-44406579-C-A is Benign according to our data. Variant chr21-44406579-C-A is described in ClinVar as [Benign]. Clinvar id is 1265082.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 rank	MANE	Protein	UniProt
TRPM2	NM_003307.4 link	c.2791-15C>A		intron_variant	Intron 18 of 31	ENST00000397928.6	NP_003298.2	O94759-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6 link	c.2791-15C>A		intron_variant	Intron 18 of 31	1	NM_003307.4	ENSP00000381023.1		O94759-1

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107695

AN:

151748

Hom.:

38674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.590

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.747

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.730

GnomAD3 exomes

AF:

0.728

AC:

172785

AN:

237226

Hom.:

63223

AF XY:

0.728

AC XY:

94196

AN XY:

129352

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.721

Gnomad EAS exome

AF:

0.791

Gnomad SAS exome

AF:

0.651

Gnomad FIN exome

AF:

0.754

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.740

GnomAD4 exome

AF:

0.748

AC:

1084843

AN:

1450394

Hom.:

407026

Cov.:

AF XY:

0.746

AC XY:

538158

AN XY:

721486

show subpopulations

Gnomad4 AFR exome

AF:

0.584

Gnomad4 AMR exome

AF:

0.722

Gnomad4 ASJ exome

AF:

0.721

Gnomad4 EAS exome

AF:

0.746

Gnomad4 SAS exome

AF:

0.655

Gnomad4 FIN exome

AF:

0.754

Gnomad4 NFE exome

AF:

0.762

Gnomad4 OTH exome

AF:

0.736

GnomAD4 genome

AF:

0.709

AC:

107728

AN:

151866

Hom.:

38674

Cov.:

AF XY:

0.707

AC XY:

52502

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.589

Gnomad4 AMR

AF:

0.747

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.650

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.729

Alfa

AF:

0.731

Hom.:

8049

Bravo

AF:

0.704

Asia WGS

AF:

0.673

AC:

2344

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

DANN

Benign

0.45

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