1-2476595-G-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001303013.1(PLCH2):c.-926G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PLCH2
NM_001303013.1 5_prime_UTR_premature_start_codon_gain
NM_001303013.1 5_prime_UTR_premature_start_codon_gain
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -2.34
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06376833).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCH2 | NM_014638.4 | c.7G>T | p.Gly3Cys | missense_variant | 1/22 | ENST00000378486.8 | NP_055453.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLCH2 | ENST00000378486.8 | c.7G>T | p.Gly3Cys | missense_variant | 1/22 | 1 | NM_014638.4 | ENSP00000367747.3 | ||
PLCH2 | ENST00000419816.6 | c.7G>T | p.Gly3Cys | missense_variant | 1/22 | 5 | ENSP00000389803.2 | |||
PLCH2 | ENST00000449969.5 | c.44-1881G>T | intron_variant | 5 | ENSP00000397289.1 | |||||
PLCH2 | ENST00000609981.5 | c.116-1881G>T | intron_variant | 5 | ENSP00000476436.1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1413634Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 700610
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1413634
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
700610
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
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 | Sep 14, 2022 | The c.7G>T (p.G3C) alteration is located in exon 1 (coding exon 1) of the PLCH2 gene. This alteration results from a G to T substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 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
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
PrimateAI
Benign
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0017);Gain of catalytic residue at M1 (P = 0.0017);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.