22-21675109-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014337.4(PPIL2):āc.289A>Gā(p.Ser97Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000682 in 1,612,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 33)
Exomes š: 0.000067 ( 0 hom. )
Consequence
PPIL2
NM_014337.4 missense
NM_014337.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
PPIL2 (HGNC:9261): (peptidylprolyl isomerase like 2) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
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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=0.012533754).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPIL2 | NM_014337.4 | c.289A>G | p.Ser97Gly | missense_variant | 6/20 | ENST00000398831.8 | NP_055152.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPIL2 | ENST00000398831.8 | c.289A>G | p.Ser97Gly | missense_variant | 6/20 | 1 | NM_014337.4 | ENSP00000381812 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000151 AC: 38AN: 251338Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135862
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GnomAD4 exome AF: 0.0000671 AC: 98AN: 1460622Hom.: 0 Cov.: 30 AF XY: 0.0000757 AC XY: 55AN XY: 726724
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152226Hom.: 0 Cov.: 33 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 | Feb 23, 2023 | The c.289A>G (p.S97G) alteration is located in exon 6 (coding exon 6) of the PPIL2 gene. This alteration results from a A to G substitution at nucleotide position 289, causing the serine (S) at amino acid position 97 to be replaced by a glycine (G). 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;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N;N
REVEL
Benign
Sift
Benign
D;D;.;T;D
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;.;B
Vest4
MVP
ClinPred
T
GERP RS
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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