chr1-2478526-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014638.4(PLCH2):c.175C>T(p.Arg59Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,542 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R59H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014638.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCH2 | NM_014638.4 | c.175C>T | p.Arg59Cys | missense_variant | 2/22 | ENST00000378486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCH2 | ENST00000378486.8 | c.175C>T | p.Arg59Cys | missense_variant | 2/22 | 1 | NM_014638.4 | P2 | |
PLCH2 | ENST00000419816.6 | c.175C>T | p.Arg59Cys | missense_variant | 2/22 | 5 | P2 | ||
PLCH2 | ENST00000449969.5 | c.94C>T | p.Arg32Cys | missense_variant | 2/22 | 5 | A2 | ||
PLCH2 | ENST00000609981.5 | c.166C>T | p.Arg56Cys | missense_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460542Hom.: 0 Cov.: 34 AF XY: 0.00000551 AC XY: 4AN XY: 726570
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2023 | The c.175C>T (p.R59C) alteration is located in exon 2 (coding exon 2) of the PLCH2 gene. This alteration results from a C to T substitution at nucleotide position 175, causing the arginine (R) at amino acid position 59 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at