chr21-44424868-A-A

Variant names:

• chr21-44424868-A-A
• NM_003307.4:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000397928.6(TRPM2):​c. variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRPM2 ENST00000397928.6 splice_donor, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.160
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397928.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM2	NM_003307.4	MANE Select	c.		intron	N/A	NP_003298.2	O94759-1
	TRPM2	NM_001320350.2		c.		intron	N/A	NP_001307279.2	E9PGK7
	TRPM2	NM_001433516.1		c.		intron	N/A	NP_001420445.1	O94759-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM2	ENST00000397928.6	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000381023.1	O94759-1
	TRPM2	ENST00000397932.6	TSL:1	c.		splice_donor intron	N/A	ENSP00000381026.2	E9PGK7
	TRPM2	ENST00000300482.9	TSL:1	c.		splice_donor intron	N/A	ENSP00000300482.5	O94759-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

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

Other links and lift over

hg19: chr21-45844751;