chr1-2479913-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014638.4(PLCH2):c.451C>T(p.Arg151Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000614 in 1,611,168 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. R151L) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
PLCH2
NM_014638.4 missense
NM_014638.4 missense
Scores
6
6
4
Clinical Significance
Conservation
PhyloP100: 6.02
Genes affected
PLCH2 (HGNC:29037): (phospholipase C eta 2) PLCH2 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave PtdIns(4,5) P2 to generate second messengers inositol 1,4,5-trisphosphate and diacylglycerol (Zhou et al., 2005 [PubMed 16107206]).[supplied by OMIM, Jun 2009]
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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 |
---|---|---|---|---|---|---|---|
PLCH2 | NM_014638.4 | c.451C>T | p.Arg151Cys | missense_variant | 3/22 | ENST00000378486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCH2 | ENST00000378486.8 | c.451C>T | p.Arg151Cys | missense_variant | 3/22 | 1 | NM_014638.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000236 AC: 36AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000587 AC: 14AN: 238682Hom.: 0 AF XY: 0.0000457 AC XY: 6AN XY: 131348
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GnomAD4 exome AF: 0.0000432 AC: 63AN: 1458824Hom.: 0 Cov.: 30 AF XY: 0.0000469 AC XY: 34AN XY: 725564
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GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.000268 AC XY: 20AN XY: 74504
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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 | Aug 16, 2022 | The c.451C>T (p.R151C) alteration is located in exon 3 (coding exon 3) of the PLCH2 gene. This alteration results from a C to T substitution at nucleotide position 451, causing the arginine (R) at amino acid position 151 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
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