22-21683215-A-G

Variant names:

• chr22-21683215-A-G
• rs763310062
• NM_014337.4:c.511A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014337.4(PPIL2):​c.511A>G​(p.Asn171Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PPIL2 NM_014337.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15693471).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	NM_014337.4	MANE Select	c.511A>G	p.Asn171Asp	missense	Exon 9 of 20	NP_055152.1	Q13356-1
	PPIL2	NM_148176.3		c.511A>G	p.Asn171Asp	missense	Exon 9 of 21	NP_680481.1	Q13356-2
	PPIL2	NM_001317996.2		c.511A>G	p.Asn171Asp	missense	Exon 9 of 21	NP_001304925.1	Q13356-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.511A>G	p.Asn171Asp	missense	Exon 9 of 20	ENSP00000381812.3	Q13356-1
	PPIL2	ENST00000626352.2	TSL:1	c.511A>G	p.Asn171Asp	missense	Exon 9 of 21	ENSP00000486725.1	Q13356-2
	PPIL2	ENST00000335025.12	TSL:1	c.511A>G	p.Asn171Asp	missense	Exon 9 of 21	ENSP00000334553.7	Q13356-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251486 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461396 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727060

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111568

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.036
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.025
Sift	Benign	0.33	T
Sift4G	Benign	0.43	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.23		Gain of ubiquitination at K176 (P = 0.0619)
MVP		0.37
ClinPred		0.53	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.54
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs763310062; hg19: chr22-22037504;