rs1255625

chr14-63498472-T-G

Variant summary

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

The NM_006246.5(PPP2R5E):c.157+41057A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,044 control chromosomes in the GnomAD database, including 12,069 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 0.32 (12069 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

Genes affected

PPP2R5E (HGNC:9313): (protein phosphatase 2 regulatory subunit B'epsilon) The protein encoded by this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A 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 epsilon isoform of the regulatory subunit B56 subfamily. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5E	NM_006246.5	c.157+41057A>C		intron_variant		ENST00000337537.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.157+41057A>C		intron_variant		1	NM_006246.5	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49248 AN: 151926 Hom.: 12036 Cov.: 32

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.324 AC: 49328 AN: 152044 Hom.: 12069 Cov.: 32 AF XY: 0.318 AC XY: 23650 AN XY: 74316

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.266

Alfa AF: 0.272 Hom.: 1020

Bravo AF: 0.340

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.59
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1255625; hg19: chr14-63965190;