8-26370124-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.1065-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,611,178 control chromosomes in the GnomAD database, including 7,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (910 hom., cov: 32)
  • Exomes 𝑓: 0.059 (6358 hom.)
• Consequence: PPP2R2A NM_002717.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001008
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.85

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=-0.9).
• BP6: Variant 8-26370124-A-G is Benign according to our data. Variant chr8-26370124-A-G is described in ClinVar as [Benign]. Clinvar id is 1679073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.1065-10A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.1065-10A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11820 AN: 151978 Hom.: 909 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0696

GnomAD3 exomes AF: 0.0863 AC: 21593 AN: 250316 Hom.: 2125 AF XY: 0.0826 AC XY: 11188 AN XY: 135396

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0693

Gnomad ASJ exome AF: 0.0577

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.0790

Gnomad FIN exome AF: 0.0792

Gnomad NFE exome AF: 0.0417

Gnomad OTH exome AF: 0.0608

GnomAD4 exome AF: 0.0592 AC: 86359 AN: 1459080 Hom.: 6358 Cov.: 31 AF XY: 0.0592 AC XY: 42982 AN XY: 725568

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0662

Gnomad4 ASJ exome AF: 0.0580

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.0811

Gnomad4 FIN exome AF: 0.0781

Gnomad4 NFE exome AF: 0.0401

Gnomad4 OTH exome AF: 0.0694

GnomAD4 genome AF: 0.0777 AC: 11825 AN: 152098 Hom.: 910 Cov.: 32 AF XY: 0.0806 AC XY: 5998 AN XY: 74386

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.0986

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0712

Alfa AF: 0.0485 Hom.: 298

Bravo AF: 0.0781

Asia WGS AF: 0.234 AC: 812 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0060
Dann	Benign	0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000010
dbscSNV1_RF	Benign	0.0
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: rs3808565; hg19: chr8-26227640; COSMIC: COSV60098344;