chr1-2480220-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014638.4(PLCH2):c.553G>A(p.Gly185Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,612,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
PLCH2
NM_014638.4 missense
NM_014638.4 missense
Scores
3
7
6
Clinical Significance
Conservation
PhyloP100: 6.56
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.553G>A | p.Gly185Arg | missense_variant | 4/22 | ENST00000378486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCH2 | ENST00000378486.8 | c.553G>A | p.Gly185Arg | missense_variant | 4/22 | 1 | NM_014638.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152234Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000764 AC: 19AN: 248744Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135104
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GnomAD4 exome AF: 0.0000561 AC: 82AN: 1460550Hom.: 0 Cov.: 33 AF XY: 0.0000564 AC XY: 41AN XY: 726552
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152234Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5AN XY: 74366
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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, 2021 | The c.553G>A (p.G185R) alteration is located in exon 4 (coding exon 4) of the PLCH2 gene. This alteration results from a G to A substitution at nucleotide position 553, causing the glycine (G) at amino acid position 185 to be replaced by an arginine (R). 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
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
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
Pathogenic
D
PROVEAN
Pathogenic
D;.;D
REVEL
Uncertain
Sift
Benign
D;.;T
Sift4G
Benign
T;T;T
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
ClinPred
T
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