21-44401911-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003307.4(TRPM2):c.2538+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,612,988 control chromosomes in the GnomAD database, including 455,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (41860 hom., cov: 32)
  • Exomes 𝑓: 0.75 (413289 hom.)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 21-44401911-C-T is Benign according to our data. Variant chr21-44401911-C-T is described in ClinVar as [Benign]. Clinvar id is 1251349.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
TRPM2	NM_003307.4	c.2538+14C>T		intron_variant		ENST00000397928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM2	ENST00000397928.6	c.2538+14C>T		intron_variant		1	NM_003307.4	P1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112593 AN: 151836 Hom.: 41845 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.750

GnomAD3 exomes AF: 0.737 AC: 184596 AN: 250366 Hom.: 68349 AF XY: 0.735 AC XY: 99634 AN XY: 135574

Gnomad AFR exome AF: 0.698

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.723

Gnomad EAS exome AF: 0.792

Gnomad SAS exome AF: 0.652

Gnomad FIN exome AF: 0.753

Gnomad NFE exome AF: 0.759

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.751 AC: 1097706 AN: 1461034 Hom.: 413289 Cov.: 49 AF XY: 0.749 AC XY: 544242 AN XY: 726802

Gnomad4 AFR exome AF: 0.700

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.751

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.754

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.741 AC: 112662 AN: 151954 Hom.: 41860 Cov.: 32 AF XY: 0.739 AC XY: 54880 AN XY: 74260

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.749

Alfa AF: 0.756 Hom.: 8303

Bravo AF: 0.741

Asia WGS AF: 0.687 AC: 2389 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.032
Dann	Benign	0.72

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: rs1785437; hg19: chr21-45821794;