Variant 5-134199106-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002715.4(PPP2CA):c.837C>T(p.Asp279Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,610,922 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 13 hom. )

Consequence

PPP2CA
NM_002715.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

PPP2CA (HGNC:9299): (protein phosphatase 2 catalytic subunit alpha) 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 an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

PPP2CA links:

ENSG00000272772 (HGNC:):

ENSG00000272772 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 5-134199106-G-A is Benign according to our data. Variant chr5-134199106-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1611135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.27 with no splicing effect.

BS2

High AC in GnomAd4 at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2CA	NM_002715.4 linkuse as main transcript	c.837C>T	p.Asp279Asp	synonymous_variant	6/7	ENST00000481195.6	NP_002706.1	P67775-1B3KUN1
PPP2CA	NM_001355019.2 linkuse as main transcript	c.642C>T	p.Asp214Asp	synonymous_variant	6/7		NP_001341948.1
PPP2CA	NR_149151.2 linkuse as main transcript	n.1092C>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPP2CA	ENST00000481195.6 linkuse as main transcript	c.837C>T	p.Asp279Asp	synonymous_variant	6/7	1	NM_002715.4	ENSP00000418447.1	P67775-1
ENSG00000272772	ENST00000519718.2 linkuse as main transcript	c.103-25084C>T		intron_variant		5		ENSP00000430774.2	E5RI56
ENSG00000273345	ENST00000703317.1 linkuse as main transcript	n.*808C>T		non_coding_transcript_exon_variant	9/10			ENSP00000515260.1	A0A8V8TQA6
ENSG00000273345	ENST00000703317.1 linkuse as main transcript	n.*808C>T		3_prime_UTR_variant	9/10			ENSP00000515260.1	A0A8V8TQA6

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00726

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00110

AC:

277

AN:

251362

Hom.:

AF XY:

0.00145

AC XY:

197

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00732

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000621

AC:

906

AN:

1458674

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

617

AN XY:

725860

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00746

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.000879

GnomAD4 genome

AF:

0.000499

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00706

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000298

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000474

ClinVar

Significance: Benign/Likely 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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 04, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	PPP2CA: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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