8-26366341-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_002717.4(PPP2R2A):c.999C>T(p.Leu333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,603,544 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (85 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1453 hom.)
• Consequence: PPP2R2A NM_002717.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.901

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 8-26366341-C-T is Benign according to our data. Variant chr8-26366341-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1679069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.901 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.999C>T	p.Leu333=	synonymous_variant	9/10	ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.999C>T	p.Leu333=	synonymous_variant	9/10	1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4667 AN: 152004 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0305

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0378

GnomAD3 exomes AF: 0.0338 AC: 8234 AN: 243542 Hom.: 192 AF XY: 0.0349 AC XY: 4609 AN XY: 131934

Gnomad AFR exome AF: 0.00775

Gnomad AMR exome AF: 0.0375

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.00186

Gnomad SAS exome AF: 0.0333

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0426

Gnomad OTH exome AF: 0.0417

GnomAD4 exome AF: 0.0421 AC: 61141 AN: 1451422 Hom.: 1453 Cov.: 30 AF XY: 0.0420 AC XY: 30293 AN XY: 721714

Gnomad4 AFR exome AF: 0.00705

Gnomad4 AMR exome AF: 0.0399

Gnomad4 ASJ exome AF: 0.0346

Gnomad4 EAS exome AF: 0.00153

Gnomad4 SAS exome AF: 0.0334

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0462

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0307 AC: 4671 AN: 152122 Hom.: 85 Cov.: 32 AF XY: 0.0303 AC XY: 2252 AN XY: 74376

Gnomad4 AFR AF: 0.00860

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0407 Hom.: 78

Bravo AF: 0.0320

Asia WGS AF: 0.0210 AC: 73 AN: 3476

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	-0.38
Cadd	Benign	4.3
Dann	Benign	0.69

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: rs34109536; hg19: chr8-26223857;