Variant 4-6372536-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020416.4(PPP2R2C):c.612C>T(p.Thr204Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,614,092 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 129 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 135 hom. )

Consequence

PPP2R2C
NM_020416.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.70

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 4-6372536-G-A is Benign according to our data. Variant chr4-6372536-G-A is described in ClinVar as [Benign]. Clinvar id is 774174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R2C	NM_020416.4 linkuse as main transcript	c.612C>T	p.Thr204Thr	synonymous_variant	5/9	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.612C>T	p.Thr204Thr	synonymous_variant	5/9	1	NM_020416.4	ENSP00000372042.4		Q9Y2T4-1

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3416

AN:

152204

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.00727

AC:

1825

AN:

251160

Hom.:

AF XY:

0.00607

AC XY:

824

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0776

Gnomad AMR exome

AF:

0.00500

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000969

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00331

AC:

4838

AN:

1461770

Hom.:

135

Cov.:

AF XY:

0.00317

AC XY:

2307

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0769

Gnomad4 AMR exome

AF:

0.00572

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00751

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000711

Gnomad4 OTH exome

AF:

0.00712

GnomAD4 genome

AF:

0.0225

AC:

3429

AN:

152322

Hom.:

129

Cov.:

AF XY:

0.0221

AC XY:

1645

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.6

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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