Genetic Variant TRPM2:c.3975-207G>A (chr21-44434924-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003307.4(TRPM2):c.3975-207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,062 control chromosomes in the GnomAD database, including 52,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.83 ( 52578 hom., cov: 32)

Consequence

TRPM2
NM_003307.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.946

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 21-44434924-G-A is Benign according to our data. Variant chr21-44434924-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277010.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM2	NM_003307.4 link	c.3975-207G>A		intron_variant	Intron 27 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.3975-207G>A		intron_variant	Intron 27 of 31	1	NM_003307.4	ENSP00000381023.1		O94759-1

Frequencies

GnomAD3 genomes

AF:

0.830

AC:

126172

AN:

151944

Hom.:

52545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.853

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.935

Gnomad SAS

AF:

0.835

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.811

Gnomad OTH

AF:

0.838

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.830

AC:

126264

AN:

152062

Hom.:

52578

Cov.:

AF XY:

0.830

AC XY:

61679

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.853

AC:

35332

AN:

41436

American (AMR)

AF:

0.842

AC:

12877

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.793

AC:

2755

AN:

3472

East Asian (EAS)

AF:

0.934

AC:

4833

AN:

5174

South Asian (SAS)

AF:

0.834

AC:

4027

AN:

4828

European-Finnish (FIN)

AF:

0.813

AC:

8607

AN:

10588

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55110

AN:

67948

Other (OTH)

AF:

0.838

AC:

1769

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1079

2158

3237

4316

5395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.815

Hom.:

31819

Bravo

AF:

0.834

Asia WGS

AF:

0.869

AC:

3023

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.99

CADD

Benign

0.20

(source)

DANN

Benign

0.35

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over