rs2838553

Positions:

• chr21-44358411-T-A

Variant summary

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

The NM_003307.4(TRPM2):​c.254+3675T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,966 control chromosomes in the GnomAD database, including 5,419 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 0.25 (5419 hom., cov: 32)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM2	NM_003307.4	c.254+3675T>A		intron_variant		ENST00000397928.6	NP_003298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6	c.254+3675T>A		intron_variant		1	NM_003307.4	ENSP00000381023.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38483 AN: 151848 Hom.: 5411 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.254 AC: 38537 AN: 151966 Hom.: 5419 Cov.: 32 AF XY: 0.251 AC XY: 18629 AN XY: 74274

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.198

Alfa AF: 0.224 Hom.: 525

Bravo AF: 0.257

Asia WGS AF: 0.168 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.80

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: rs2838553; hg19: chr21-45778294;