8-26360759-A-T

Position:

• chr8-26360759-A-T

Variant summary

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

The NM_002717.4(PPP2R2A):​c.460-215A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 488,364 control chromosomes in the GnomAD database, including 822 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 0.045 (190 hom., cov: 32)
  • Exomes 𝑓: 0.051 (632 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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=-0.84).
• 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.460-215A>T		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.460-215A>T		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6872 AN: 152204 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0513 AC: 17236 AN: 336042 Hom.: 632 Cov.: 4 AF XY: 0.0539 AC XY: 9396 AN XY: 174314

Gnomad4 AFR exome AF: 0.0292

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.000305

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0659

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0510

GnomAD4 genome AF: 0.0452 AC: 6884 AN: 152322 Hom.: 190 Cov.: 32 AF XY: 0.0475 AC XY: 3534 AN XY: 74478

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0475 Hom.: 17

Bravo AF: 0.0384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.68

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: rs17309529; hg19: chr8-26218275;