3-136001753-C-G

Variant names:

• chr3-136001753-C-G
• NM_002718.5:c.255C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002718.5(PPP2R3A):​c.255C>G​(p.Asp85Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP2R3A NM_002718.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620

Genes affected

PPP2R3A (HGNC:9307): (protein phosphatase 2 regulatory subunit B''alpha) This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06541541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3A	NM_002718.5	c.255C>G	p.Asp85Glu	missense_variant	Exon 2 of 14	ENST00000264977.8	NP_002709.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3A	ENST00000264977.8	c.255C>G	p.Asp85Glu	missense_variant	Exon 2 of 14	1	NM_002718.5	ENSP00000264977.3
PPP2R3A	ENST00000490467.5	c.-213-25079C>G		intron_variant	Intron 1 of 12	2		ENSP00000419344.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.255C>G (p.D85E) alteration is located in exon 2 (coding exon 1) of the PPP2R3A gene. This alteration results from a C to G substitution at nucleotide position 255, causing the aspartic acid (D) at amino acid position 85 to be replaced by a glutamic acid (E). 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	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.4
DANN	Benign	0.96
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.0070
Sift	Benign	0.24	T
Sift4G	Benign	0.34	T
Polyphen		0.058	B
Vest4		0.060
MutPred		0.31		Gain of solvent accessibility (P = 0.1014);
MVP		0.10
MPC		0.36
ClinPred		0.35	T
GERP RS		2.7
Varity_R		0.037
gMVP		0.069

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: chr3-135720595;