rs3824232

chr8-26370083-A-Cchr8-26370083-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002717.4(PPP2R2A):c.1065-51A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,557,578 control chromosomes in the GnomAD database, including 21,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3207 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18009 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-26370083-A-C is Benign according to our data. Variant chr8-26370083-A-C is described in ClinVar as [Benign]. Clinvar id is 1679072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.1065-51A>C		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.1065-51A>C		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28336 AN: 152000 Hom.: 3207 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.168 AC: 38415 AN: 228572 Hom.: 4018 AF XY: 0.163 AC XY: 20209 AN XY: 123882

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.423

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.148 AC: 207801 AN: 1405458 Hom.: 18009 Cov.: 29 AF XY: 0.147 AC XY: 102362 AN XY: 695402

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.186 AC: 28354 AN: 152120 Hom.: 3207 Cov.: 32 AF XY: 0.186 AC XY: 13821 AN XY: 74360

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.181

Alfa AF: 0.153 Hom.: 438

Bravo AF: 0.191

Asia WGS AF: 0.276 AC: 959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary breast ovarian cancer syndrome Benign:1

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	-0.81
Cadd	Benign	3.0
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs3824232; hg19: chr8-26227599; COSMIC: COSV60098826;