22-21675109-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014337.4(PPIL2):ā€‹c.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

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73
Variant links:
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]

Genome browser will be placed here

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
PPIL2NM_014337.4 linkuse as main transcriptc.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
PPIL2ENST00000398831.8 linkuse as main transcriptc.289A>G p.Ser97Gly missense_variant 6/201 NM_014337.4 ENSP00000381812 P1Q13356-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000151
AC:
38
AN:
251338
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00338
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000671
AC:
98
AN:
1460622
Hom.:
0
Cov.:
30
AF XY:
0.0000757
AC XY:
55
AN XY:
726724
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00272
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152226
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000315
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsFeb 23, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;T;.;T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.039
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.96
.;.;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.013
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
M;M;M;.;M
MutationTaster
Benign
0.92
D;D;D;D;D;D
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.9
N;N;.;N;N
REVEL
Benign
0.024
Sift
Benign
0.046
D;D;.;T;D
Sift4G
Benign
0.17
T;T;T;T;T
Polyphen
0.0040
B;B;B;.;B
Vest4
0.28
MVP
0.42
ClinPred
0.094
T
GERP RS
4.6
Varity_R
0.059
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370015532; hg19: chr22-22029398; API