chr21-44364258-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_003307.4(TRPM2):c.399G>A(p.Thr133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,614,166 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 51 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 45 hom. )
Consequence
TRPM2
NM_003307.4 synonymous
NM_003307.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.63
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 21-44364258-G-A is Benign according to our data. Variant chr21-44364258-G-A is described in ClinVar as [Benign]. Clinvar id is 785674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.63 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM2 | NM_003307.4 | c.399G>A | p.Thr133= | synonymous_variant | 3/32 | ENST00000397928.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM2 | ENST00000397928.6 | c.399G>A | p.Thr133= | synonymous_variant | 3/32 | 1 | NM_003307.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0156 AC: 2380AN: 152202Hom.: 53 Cov.: 33
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GnomAD3 exomes AF: 0.00430 AC: 1080AN: 251436Hom.: 24 AF XY: 0.00299 AC XY: 406AN XY: 135898
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GnomAD4 exome AF: 0.00160 AC: 2338AN: 1461846Hom.: 45 Cov.: 31 AF XY: 0.00139 AC XY: 1009AN XY: 727220
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GnomAD4 genome AF: 0.0156 AC: 2380AN: 152320Hom.: 51 Cov.: 33 AF XY: 0.0146 AC XY: 1090AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at