rs1612472

Positions:

• chr21-44413102-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003307.4(TRPM2):​c.2963-789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,862 control chromosomes in the GnomAD database, including 38,477 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 0.71 (38477 hom., cov: 31)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM2	NM_003307.4	c.2963-789C>T		intron_variant		ENST00000397928.6	NP_003298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6	c.2963-789C>T		intron_variant		1	NM_003307.4	ENSP00000381023	P1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107316 AN: 151744 Hom.: 38475 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.707 AC: 107356 AN: 151862 Hom.: 38477 Cov.: 31 AF XY: 0.705 AC XY: 52352 AN XY: 74224

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.726

Alfa AF: 0.732 Hom.: 9074

Bravo AF: 0.700

Asia WGS AF: 0.677 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs1612472; hg19: chr21-45832985;