Genetic Variant PPIL2:p.Asp147Asp (chr22-21682490-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP7

The NM_014337.4(PPIL2):c.441C>T(p.Asp147Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,602,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PPIL2
NM_014337.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.251

Publications

0 publications found

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]

PPIL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=-0.251 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014337.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPIL2	NM_014337.4	MANE Select	c.441C>T	p.Asp147Asp	synonymous	Exon 8 of 20	NP_055152.1	Q13356-1
PPIL2	NM_148176.3		c.441C>T	p.Asp147Asp	synonymous	Exon 8 of 21	NP_680481.1	Q13356-2
PPIL2	NM_001317996.2		c.441C>T	p.Asp147Asp	synonymous	Exon 8 of 21	NP_001304925.1	Q13356-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.441C>T	p.Asp147Asp	synonymous	Exon 8 of 20	ENSP00000381812.3	Q13356-1
PPIL2	ENST00000626352.2	TSL:1	c.441C>T	p.Asp147Asp	synonymous	Exon 8 of 21	ENSP00000486725.1	Q13356-2
PPIL2	ENST00000335025.12	TSL:1	c.441C>T	p.Asp147Asp	synonymous	Exon 8 of 21	ENSP00000334553.7	Q13356-1

Frequencies

GnomAD3 genomes

AF:

0.0000900

AC:

AN:

144498

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251076

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1457470

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724964

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33392

American (AMR)

AF:

0.0000225

AC:

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.000127

AC:

AN:

39374

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1109540

Other (OTH)

AF:

0.0000166

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000899

AC:

AN:

144604

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

70550

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

39458

American (AMR)

AF:

0.00

AC:

AN:

14258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3342

East Asian (EAS)

AF:

0.00

AC:

AN:

4846

South Asian (SAS)

AF:

0.00

AC:

AN:

4476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65292

Other (OTH)

AF:

0.00

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.3

(source)

DANN

Benign

0.86

PhyloP100

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over