rs17309613

Positions:

• chr8-26363084-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002717.4(PPP2R2A):​c.802+236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 397,138 control chromosomes in the GnomAD database, including 747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.039 (177 hom., cov: 31)
  • Exomes 𝑓: 0.054 (570 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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+236T>C		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.802+236T>C		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5977 AN: 152056 Hom.: 178 Cov.: 31

Gnomad AFR AF: 0.00947

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0536 AC: 13142 AN: 244964 Hom.: 570 Cov.: 4 AF XY: 0.0584 AC XY: 7429 AN XY: 127304

Gnomad4 AFR exome AF: 0.00821

Gnomad4 AMR exome AF: 0.0239

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.000343

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0673

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.0527

GnomAD4 genome AF: 0.0393 AC: 5976 AN: 152174 Hom.: 177 Cov.: 31 AF XY: 0.0415 AC XY: 3089 AN XY: 74404

Gnomad4 AFR AF: 0.00944

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0515 Hom.: 112

Bravo AF: 0.0319

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.61

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: rs17309613; hg19: chr8-26220600;