8-30799716-C-T

Variant names:

• chr8-30799716-C-T
• NM_001009552.2:c.142G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009552.2(PPP2CB):​c.142G>A​(p.Val48Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP2CB NM_001009552.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

PPP2CB (HGNC:9300): (protein phosphatase 2 catalytic subunit beta) This gene encodes the phosphatase 2A catalytic subunit. 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. This gene encodes a beta isoform of the catalytic subunit. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23353994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2CB	NM_001009552.2	c.142G>A	p.Val48Ile	missense_variant	Exon 2 of 7	ENST00000221138.9	NP_001009552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2CB	ENST00000221138.9	c.142G>A	p.Val48Ile	missense_variant	Exon 2 of 7	1	NM_001009552.2	ENSP00000221138.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142G>A (p.V48I) alteration is located in exon 2 (coding exon 2) of the PPP2CB gene. This alteration results from a G to A substitution at nucleotide position 142, causing the valine (V) at amino acid position 48 to be replaced by an isoleucine (I). 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	0.16
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.089
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.098
Sift	Benign	0.038	D
Sift4G	Benign	0.22	T
Polyphen		0.0040	B
Vest4		0.40
MutPred		0.39		Loss of loop (P = 0.1242);
MVP		0.44
MPC		0.65
ClinPred		0.86	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.27

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: chr8-30657232;