NM_001352913.2:c.880_882delCTAinsGTG

Variant names:

• chr14-101893025-CTA-GTG
• NM_001352913.2:c.880_882delCTAinsGTG
• PPP2R5C p.Leu294Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001352913.2(PPP2R5C):​c.880_882delCTAinsGTG​(p.Leu294Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP2R5C NM_001352913.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	NM_001352913.2	MANE Select	c.880_882delCTAinsGTG	p.Leu294Val	missense	N/A	NP_001339842.1	A0A8Q3WKR3
	PPP2R5C	NM_001161725.2		c.808_810delCTAinsGTG	p.Leu270Val	missense	N/A	NP_001155197.1	Q13362-5
	PPP2R5C	NM_001352914.2		c.895_897delCTAinsGTG	p.Leu299Val	missense	N/A	NP_001339843.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	ENST00000694906.1	MANE Select	c.880_882delCTAinsGTG	p.Leu294Val	missense	N/A	ENSP00000511581.1	A0A8Q3WKR3
	PPP2R5C	ENST00000334743.9	TSL:1	c.715_717delCTAinsGTG	p.Leu239Val	missense	N/A	ENSP00000333905.4	Q13362-1
	PPP2R5C	ENST00000350249.7	TSL:1	c.715_717delCTAinsGTG	p.Leu239Val	missense	N/A	ENSP00000262239.5	Q13362-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-102359362;