Variant 4-6381080-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020416.4(PPP2R2C):c.85A>G(p.Thr29Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PPP2R2C
NM_020416.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Variant links:

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]

PPP2R2C links:

PPP2R2C (HGNC:):

PPP2R2C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2C	NM_020416.4 linkuse as main transcript	c.85A>G	p.Thr29Ala	missense_variant	2/9	ENST00000382599.9	NP_065149.2	Q9Y2T4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2C	ENST00000382599.9 linkuse as main transcript	c.85A>G	p.Thr29Ala	missense_variant	2/9	1	NM_020416.4	ENSP00000372042.4		Q9Y2T4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441688

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.85A>G (p.T29A) alteration is located in exon 2 (coding exon 2) of the PPP2R2C gene. This alteration results from a A to G substitution at nucleotide position 85, causing the threonine (T) at amino acid position 29 to be replaced by an alanine (A). 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

0.081

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Benign

0.63

DEOGEN2

Benign

0.11

.;.;.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;.;D;D;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.68

D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.31

N;.;.;N;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.61

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.022

B;.;B;B;.

Vest4

0.89

MutPred

0.58

Loss of glycosylation at T29 (P = 0.0832);.;.;Loss of glycosylation at T29 (P = 0.0832);.;

MVP

0.86

MPC

1.2

ClinPred

0.51

GERP RS

4.3

Varity_R

0.18

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over