8-26362926-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.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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

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=-0.84).
• 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_single_submitter, 1 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	c.802+78A>G		intron_variant		ENST00000380737.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5981 AN: 152180 Hom.: 175 Cov.: 31

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.: 17 AF XY: 0.0562 AC XY: 34878 AN XY: 620108

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.: 31 AF XY: 0.0415 AC XY: 3088 AN XY: 74468

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.: 27

Bravo AF: 0.0319

Asia WGS AF: 0.0470 AC: 165 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	-0.84
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

Other links and lift over

dbSNP: rs17309592; hg19: chr8-26220442;