chr21-44369195-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003307.4(TRPM2):āc.623G>Cā(p.Gly208Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,611,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 33)
Exomes š: 0.000038 ( 0 hom. )
Consequence
TRPM2
NM_003307.4 missense
NM_003307.4 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 5.58
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM2 | NM_003307.4 | c.623G>C | p.Gly208Ala | missense_variant | 5/32 | ENST00000397928.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM2 | ENST00000397928.6 | c.623G>C | p.Gly208Ala | missense_variant | 5/32 | 1 | NM_003307.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000574 AC: 14AN: 243928Hom.: 0 AF XY: 0.0000680 AC XY: 9AN XY: 132408
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GnomAD4 exome AF: 0.0000377 AC: 55AN: 1458926Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 26AN XY: 725694
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 09, 2022 | The c.623G>C (p.G208A) alteration is located in exon 5 (coding exon 5) of the TRPM2 gene. This alteration results from a G to C substitution at nucleotide position 623, causing the glycine (G) at amino acid position 208 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Benign
T;T;T;D
Polyphen
D;D;D;.
Vest4
MVP
MPC
0.64
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at