chr22-21682490-C-G

Position:

• chr22-21682490-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014337.4(PPIL2):​c.441C>G​(p.Asp147Glu) variant causes a missense 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: 33)
• Consequence: PPIL2 NM_014337.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.251

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3589545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIL2	NM_014337.4	c.441C>G	p.Asp147Glu	missense_variant	8/20	ENST00000398831.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIL2	ENST00000398831.8	c.441C>G	p.Asp147Glu	missense_variant	8/20	1	NM_014337.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.441C>G (p.D147E) alteration is located in exon 8 (coding exon 8) of the PPIL2 gene. This alteration results from a C to G substitution at nucleotide position 441, causing the aspartic acid (D) at amino acid position 147 to be replaced by a glutamic acid (E). 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	0.32
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.2
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.97	.;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.0	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.4	D;D;.;D
REVEL	Benign	0.28
Sift	Uncertain	0.029	D;D;.;D
Sift4G	Benign	0.064	T;T;D;T
Polyphen		0.99	D;D;P;D
Vest4		0.51
MutPred		0.46		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.33
ClinPred		0.99	D
GERP RS		-5.4
Varity_R		0.32
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs755435729; hg19: chr22-22036779; COSMIC: COSV58604622; COSMIC: COSV58604622;