NM_001352913.2:c.880C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 2 publications found

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]

PPP2R5C Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352913.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	NM_001352913.2	MANE Select	c.880C>G	p.Leu294Val	missense	Exon 9 of 16	NP_001339842.1
	PPP2R5C	NM_001161725.2		c.808C>G	p.Leu270Val	missense	Exon 9 of 16	NP_001155197.1
	PPP2R5C	NM_001352914.2		c.895C>G	p.Leu299Val	missense	Exon 9 of 15	NP_001339843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	ENST00000694906.1	MANE Select	c.880C>G	p.Leu294Val	missense	Exon 9 of 16	ENSP00000511581.1
	PPP2R5C	ENST00000334743.9	TSL:1	c.715C>G	p.Leu239Val	missense	Exon 7 of 14	ENSP00000333905.4
	PPP2R5C	ENST00000350249.7	TSL:1	c.715C>G	p.Leu239Val	missense	Exon 7 of 13	ENSP00000262239.5

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

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		1.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.70		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
Mutation Taster		=42/58	disease causing

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

Other links and lift over

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