8-26293797-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002717.4(PPP2R2A):c.82+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,499,618 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (50 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0820

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-26293797-A-G is Benign according to our data. Variant chr8-26293797-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1679063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 421 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.82+57A>G		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.82+57A>G		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.00277 AC: 421 AN: 152216 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00512 AC: 1213 AN: 236958 Hom.: 11 AF XY: 0.00577 AC XY: 743 AN XY: 128702

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.00219

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0139

Gnomad FIN exome AF: 0.00274

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.00720

GnomAD4 exome AF: 0.00363 AC: 4887 AN: 1347284 Hom.: 50 Cov.: 20 AF XY: 0.00407 AC XY: 2754 AN XY: 676180

Gnomad4 AFR exome AF: 0.000520

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.0315

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.00228

Gnomad4 NFE exome AF: 0.00238

Gnomad4 OTH exome AF: 0.00557

GnomAD4 genome AF: 0.00274 AC: 418 AN: 152334 Hom.: 5 Cov.: 32 AF XY: 0.00271 AC XY: 202 AN XY: 74488

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00495 Hom.: 2

Bravo AF: 0.00270

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.4
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs372615585; hg19: chr8-26151313; COSMIC: COSV105879852; COSMIC: COSV105879852;