chr1-2476671-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_014638.4(PLCH2):c.83G>C(p.Gly28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,610,838 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0023 ( 15 hom., cov: 34)
Exomes 𝑓: 0.0023 ( 132 hom. )
Consequence
PLCH2
NM_014638.4 missense
NM_014638.4 missense
Scores
1
13
Clinical Significance
Conservation
PhyloP100: 2.53
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.002139032).
BP6
?
Variant 1-2476671-G-C is Benign according to our data. Variant chr1-2476671-G-C is described in ClinVar as [Benign]. Clinvar id is 779852.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCH2 | NM_014638.4 | c.83G>C | p.Gly28Ala | missense_variant | 1/22 | ENST00000378486.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCH2 | ENST00000378486.8 | c.83G>C | p.Gly28Ala | missense_variant | 1/22 | 1 | NM_014638.4 | P2 | |
PLCH2 | ENST00000419816.6 | c.83G>C | p.Gly28Ala | missense_variant | 1/22 | 5 | P2 | ||
PLCH2 | ENST00000449969.5 | c.44-1805G>C | intron_variant | 5 | A2 | ||||
PLCH2 | ENST00000609981.5 | c.116-1805G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00231 AC: 352AN: 152200Hom.: 15 Cov.: 34
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GnomAD3 exomes AF: 0.00468 AC: 1136AN: 242944Hom.: 29 AF XY: 0.00429 AC XY: 569AN XY: 132528
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GnomAD4 exome AF: 0.00227 AC: 3312AN: 1458520Hom.: 132 Cov.: 31 AF XY: 0.00220 AC XY: 1599AN XY: 725442
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GnomAD4 genome ? AF: 0.00230 AC: 350AN: 152318Hom.: 15 Cov.: 34 AF XY: 0.00248 AC XY: 185AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
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