2-169630791-A-G

Variant names:

• chr2-169630791-A-G
• rs1002294715
• NM_004792.3:c.565A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004792.3(PPIG):​c.565A>G​(p.Lys189Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000416 in 1,443,900 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PPIG NM_004792.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60

Genes affected

PPIG (HGNC:14650): (peptidylprolyl isomerase G) Enables cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Involved in protein peptidyl-prolyl isomerization. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.565A>G	p.Lys189Glu	missense_variant	Exon 10 of 14	ENST00000260970.8	NP_004783.2
PPIG	XM_005246966.3	c.565A>G	p.Lys189Glu	missense_variant	Exon 10 of 14		XP_005247023.1
PPIG	XM_005246967.2	c.565A>G	p.Lys189Glu	missense_variant	Exon 10 of 14		XP_005247024.1
PPIG	XM_017005302.3	c.565A>G	p.Lys189Glu	missense_variant	Exon 10 of 12		XP_016860791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.565A>G	p.Lys189Glu	missense_variant	Exon 10 of 14	1	NM_004792.3	ENSP00000260970.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000416 AC: 6 AN: 1443900 Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3 AN XY: 717794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;T;T;.;T;T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.2	L;.;.;L;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.043	D;T;T;T;D;T
Sift4G	Benign	0.071	T;D;T;T;T;T
Polyphen		0.99	D;D;D;D;D;.
Vest4		0.37
MutPred		0.32		Loss of methylation at K189 (P = 2e-04);.;.;Loss of methylation at K189 (P = 2e-04);Loss of methylation at K189 (P = 2e-04);Loss of methylation at K189 (P = 2e-04);
MVP		0.23
MPC		1.2
ClinPred		0.96	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.56

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: rs1002294715; hg19: chr2-170487301;