chr22-21683254-C-T

Variant names:

• chr22-21683254-C-T
• rs2067207024
• NM_014337.4:c.550C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014337.4(PPIL2):​c.550C>T​(p.Pro184Ser) variant causes a missense change. 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: 4.85

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14888027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIL2	NM_014337.4	c.550C>T	p.Pro184Ser	missense_variant	Exon 9 of 20	ENST00000398831.8	NP_055152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIL2	ENST00000398831.8	c.550C>T	p.Pro184Ser	missense_variant	Exon 9 of 20	1	NM_014337.4	ENSP00000381812.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550C>T (p.P184S) alteration is located in exon 9 (coding exon 9) of the PPIL2 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the proline (P) at amino acid position 184 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T;T;.;T
Eigen	Benign	0.017
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	.;.;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;L;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.90	N;N;.;N
REVEL	Benign	0.11
Sift	Benign	0.24	T;T;.;T
Sift4G	Benign	0.44	T;T;T;T
Polyphen		0.37	B;B;B;B
Vest4		0.40
MutPred		0.25		Gain of phosphorylation at P184 (P = 0.0596);Gain of phosphorylation at P184 (P = 0.0596);Gain of phosphorylation at P184 (P = 0.0596);Gain of phosphorylation at P184 (P = 0.0596);
MVP		0.45
ClinPred		0.84	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.094
gMVP		0.47

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: rs2067207024; hg19: chr22-22037543;