Variant 8-26362926-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002717.4(PPP2R2A):c.802+78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,392,080 control chromosomes in the GnomAD database, including 2,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 174 hom., cov: 31)

Exomes 𝑓: 0.053 ( 2300 hom. )

Consequence

PPP2R2A
NM_002717.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-26362926-A-G is Benign according to our data. Variant chr8-26362926-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1679066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 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.802+78A>G		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8 linkuse as main transcript	c.802+78A>G		intron_variant		1	NM_002717.4	P1	P63151-1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5981

AN:

152180

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00924

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0679

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0493

Gnomad OTH

AF:

0.0296

GnomAD4 exome

AF:

0.0531

AC:

65840

AN:

1239782

Hom.:

2300

Cov.:

AF XY:

0.0562

AC XY:

34878

AN XY:

620108

show subpopulations

Gnomad4 AFR exome

AF:

0.00770

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.000275

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.0686

Gnomad4 NFE exome

AF:

0.0491

Gnomad4 OTH exome

AF:

0.0554

GnomAD4 genome

AF:

0.0393

AC:

5980

AN:

152298

Hom.:

174

Cov.:

AF XY:

0.0415

AC XY:

3088

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00922

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0679

Gnomad4 NFE

AF:

0.0493

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0444

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.0470

AC:

165

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.84

CADD

Benign

1.0

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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