Variant 4-6323471-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_020416.4(PPP2R2C):c.1175G>A(p.Arg392His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PPP2R2C
NM_020416.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28853744).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2C	NM_020416.4 linkuse as main transcript	c.1175G>A	p.Arg392His	missense_variant	9/9	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.1175G>A	p.Arg392His	missense_variant	9/9	1	NM_020416.4	ENSP00000372042.4		Q9Y2T4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460402

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726168

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:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Nov 13, 2024

The c.1175G>A (p.R392H) alteration is located in exon 9 (coding exon 9) of the PPP2R2C gene. This alteration results from a G to A substitution at nucleotide position 1175, causing the arginine (R) at amino acid position 392 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;.;.;T;.

Eigen

Benign

-0.099

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.97

D;.;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;.;L;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.040

D;D;D;D;D

Sift4G

Uncertain

0.051

T;D;T;T;D

Polyphen

0.010

B;.;B;B;.

Vest4

0.32

MutPred

0.51

Loss of MoRF binding (P = 0.0342);.;.;Loss of MoRF binding (P = 0.0342);.;

MVP

0.85

MPC

1.4

ClinPred

0.76

GERP RS

4.3

Varity_R

0.18

gMVP

0.52

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

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