Variant chr8-26366341-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002717.4(PPP2R2A):c.999C>T(p.Leu333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,603,544 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 85 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1453 hom. )

Consequence

PPP2R2A
NM_002717.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.901

Variant links:

Genes affected

PPP2R2A (HGNC:9304): (protein phosphatase 2 regulatory subunit Balpha) 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 an alpha isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 8-26366341-C-T is Benign according to our data. Variant chr8-26366341-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1679069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.901 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4 linkuse as main transcript	c.999C>T	p.Leu333=	synonymous_variant	9/10	ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8 linkuse as main transcript	c.999C>T	p.Leu333=	synonymous_variant	9/10	1	NM_002717.4	P1	P63151-1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4667

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00862

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.0305

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0338

AC:

8234

AN:

243542

Hom.:

192

AF XY:

0.0349

AC XY:

4609

AN XY:

131934

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.0375

Gnomad ASJ exome

AF:

0.0339

Gnomad EAS exome

AF:

0.00186

Gnomad SAS exome

AF:

0.0333

Gnomad FIN exome

AF:

0.0266

Gnomad NFE exome

AF:

0.0426

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

AF:

0.0421

AC:

61141

AN:

1451422

Hom.:

1453

Cov.:

AF XY:

0.0420

AC XY:

30293

AN XY:

721714

show subpopulations

Gnomad4 AFR exome

AF:

0.00705

Gnomad4 AMR exome

AF:

0.0399

Gnomad4 ASJ exome

AF:

0.0346

Gnomad4 EAS exome

AF:

0.00153

Gnomad4 SAS exome

AF:

0.0334

Gnomad4 FIN exome

AF:

0.0258

Gnomad4 NFE exome

AF:

0.0462

Gnomad4 OTH exome

AF:

0.0423

GnomAD4 genome

AF:

0.0307

AC:

4671

AN:

152122

Hom.:

Cov.:

AF XY:

0.0303

AC XY:

2252

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00860

Gnomad4 AMR

AF:

0.0340

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.0307

Gnomad4 FIN

AF:

0.0254

Gnomad4 NFE

AF:

0.0449

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0407

Hom.:

Bravo

AF:

0.0320

Asia WGS

AF:

0.0210

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.3

DANN

Benign

0.69

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