8-26339117-A-T

Variant names:

• chr8-26339117-A-T
• rs3808573
• NM_002717.4:c.180+130A>T

Variant summary

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

The NM_002717.4(PPP2R2A):​c.180+130A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 661,562 control chromosomes in the GnomAD database, including 14,985 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 0.21 (3709 hom., cov: 32)
  • Exomes 𝑓: 0.20 (11276 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4	c.180+130A>T		intron_variant	Intron 3 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.180+130A>T		intron_variant	Intron 3 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32173 AN: 152006 Hom.: 3704 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.196 AC: 99899 AN: 509438 Hom.: 11276 AF XY: 0.195 AC XY: 52732 AN XY: 270694

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.212 AC: 32201 AN: 152124 Hom.: 3709 Cov.: 32 AF XY: 0.212 AC XY: 15781 AN XY: 74350

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.218

Alfa AF: 0.187 Hom.: 336

Bravo AF: 0.217

Asia WGS AF: 0.296 AC: 1028 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.62
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: rs3808573; hg19: chr8-26196633;