Genetic Variant TRPM2:c.3147-1805C>T (chr21-44416122-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003307.4(TRPM2):c.3147-1805C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,242 control chromosomes in the GnomAD database, including 42,987 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 42938 hom., cov: 31)

Exomes 𝑓: 0.71 ( 49 hom. )

Consequence

TRPM2
NM_003307.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

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:

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

TRPM2-AS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003307.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRPM2	NM_003307.4	MANE Select	c.3147-1805C>T	intron	N/A	NP_003298.2
TRPM2	NM_001320350.2		c.3147-1805C>T	intron	N/A	NP_001307279.2
TRPM2	NM_001433516.1		c.3147-1805C>T	intron	N/A	NP_001420445.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRPM2	ENST00000397928.6	TSL:1 MANE Select	c.3147-1805C>T	intron	N/A	ENSP00000381023.1
TRPM2	ENST00000397932.6	TSL:1	c.3147-1805C>T	intron	N/A	ENSP00000381026.2
TRPM2	ENST00000300482.9	TSL:1	c.3147-1805C>T	intron	N/A	ENSP00000300482.5

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114088

AN:

151930

Hom.:

42920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.711

AC:

138

AN:

194

Hom.:

Cov.:

AF XY:

0.688

AC XY:

106

AN XY:

154

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.719

AC:

115

AN:

160

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.751

AC:

114155

AN:

152048

Hom.:

42938

Cov.:

AF XY:

0.750

AC XY:

55705

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.720

AC:

29828

AN:

41428

American (AMR)

AF:

0.780

AC:

11931

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

2494

AN:

3472

East Asian (EAS)

AF:

0.806

AC:

4167

AN:

5172

South Asian (SAS)

AF:

0.669

AC:

3226

AN:

4822

European-Finnish (FIN)

AF:

0.752

AC:

7946

AN:

10564

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.766

AC:

52065

AN:

67980

Other (OTH)

AF:

0.760

AC:

1607

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1451

2901

4352

5802

7253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.768

Hom.:

5587

Bravo

AF:

0.752

Asia WGS

AF:

0.711

AC:

2476

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.073

(source)

DANN

Benign

0.32

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over