rs17309515

Positions:

• chr8-26360340-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002717.4(PPP2R2A):​c.459+59A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 965,884 control chromosomes in the GnomAD database, including 1,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (194 hom., cov: 32)
  • Exomes 𝑓: 0.053 (1658 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.302

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-26360340-A-C is Benign according to our data. Variant chr8-26360340-A-C is described in ClinVar as [Benign]. Clinvar id is 1679064.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	Protein	UniProt
PPP2R2A	NM_002717.4	c.459+59A>C		intron_variant		ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.459+59A>C		intron_variant		1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6876 AN: 152166 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0532 AC: 43276 AN: 813600 Hom.: 1658 AF XY: 0.0566 AC XY: 23972 AN XY: 423872

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.000195

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0690

Gnomad4 NFE exome AF: 0.0473

Gnomad4 OTH exome AF: 0.0554

GnomAD4 genome AF: 0.0452 AC: 6888 AN: 152284 Hom.: 194 Cov.: 32 AF XY: 0.0475 AC XY: 3537 AN XY: 74466

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.0282

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: 0.0341

Alfa AF: 0.0466 Hom.: 33

Bravo AF: 0.0384

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

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	2.1
DANN	Benign	0.57

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: rs17309515; hg19: chr8-26217856;