rs193920829

Variant names:

• chr14-101893025-C-G
• rs193920829
• NM_001352913.2:c.880C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001352913.2(PPP2R5C):​c.880C>G​(p.Leu294Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP2R5C NM_001352913.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.03

Genes affected

PPP2R5C (HGNC:9311): (protein phosphatase 2 regulatory subunit B'gamma) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a gamma isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5C	NM_001352913.2	c.880C>G	p.Leu294Val	missense_variant	Exon 9 of 16	ENST00000694906.1	NP_001339842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5C	ENST00000694906.1	c.880C>G	p.Leu294Val	missense_variant	Exon 9 of 16		NM_001352913.2	ENSP00000511581.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	.;.;.;.;D;.;D;D;D
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.9	.;.;.;H;.;H;H;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D;D;D
Polyphen		1.0, 0.99, 0.99	.;.;.;D;.;D;D;.;.
Vest4		0.72
MutPred		0.70		.;.;.;Gain of catalytic residue at A236 (P = 2e-04);.;Gain of catalytic residue at A236 (P = 2e-04);Gain of catalytic residue at A236 (P = 2e-04);Gain of catalytic residue at A236 (P = 2e-04);.;
MVP		0.80
MPC		2.2
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920829; hg19: chr14-102359362; COSMIC: COSV58277052;