4-6323431-A-C

Position:

• chr4-6323431-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020416.4(PPP2R2C):​c.1215T>G​(p.Ser405Arg) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP2R2C NM_020416.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

Genes affected

PPP2R2C (HGNC:9306): (protein phosphatase 2 regulatory subunit Bgamma) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 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 B55 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30166754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2C	NM_020416.4	c.1215T>G	p.Ser405Arg	missense_variant	9/9	ENST00000382599.9	NP_065149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2C	ENST00000382599.9	c.1215T>G	p.Ser405Arg	missense_variant	9/9	1	NM_020416.4	ENSP00000372042.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.1215T>G (p.S405R) alteration is located in exon 9 (coding exon 9) of the PPP2R2C gene. This alteration results from a T to G substitution at nucleotide position 1215, causing the serine (S) at amino acid position 405 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;.;.;T;.
Eigen	Benign	0.083
Eigen_PC	Benign	-0.0073
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.95	D;.;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M;.;.;M;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.023	D;D;D;D;D
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.95	P;.;P;P;.
Vest4		0.41
MutPred		0.37		Gain of MoRF binding (P = 0.014);.;.;Gain of MoRF binding (P = 0.014);.;
MVP		0.78
MPC		2.3
ClinPred		0.97	D
GERP RS		0.83
Varity_R		0.43
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-6325158;