ENST00000626352.2:c.1561A>C

Variant names:

• chr22-21695492-A-C
• ENST00000626352.2:c.1561A>C
• PPIL2 p.Ser521Arg

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000626352.2(PPIL2):​c.1561A>C​(p.Ser521Arg) 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. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S521S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPIL2 ENST00000626352.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037886083).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000626352.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	NM_014337.4	MANE Select	c.*2A>C		3_prime_UTR	Exon 20 of 20	NP_055152.1	Q13356-1
	PPIL2	NM_148176.3		c.1561A>C	p.Ser521Arg	missense	Exon 20 of 21	NP_680481.1	Q13356-2
	PPIL2	NM_001317996.2		c.*2A>C		3_prime_UTR	Exon 20 of 21	NP_001304925.1	Q13356-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	ENST00000626352.2	TSL:1	c.1561A>C	p.Ser521Arg	missense	Exon 20 of 21	ENSP00000486725.1	Q13356-2
	PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.*2A>C		3_prime_UTR	Exon 20 of 20	ENSP00000381812.3	Q13356-1
	PPIL2	ENST00000335025.12	TSL:1	c.*2A>C		3_prime_UTR	Exon 20 of 21	ENSP00000334553.7	Q13356-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Uncertain	0.98
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.20
PrimateAI	Benign	0.36	T
Sift4G	Uncertain	0.029	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.39
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-22049781;