14-63434576-C-T

Variant names:

• chr14-63434576-C-T
• rs10140679
• NM_006246.5:c.355-12482G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337537.8(PPP2R5E):​c.355-12482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,002 control chromosomes in the GnomAD database, including 18,546 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 0.43 (18546 hom., cov: 32)
• Consequence: PPP2R5E ENST00000337537.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000337537.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	NM_006246.5	MANE Select	c.355-12482G>A		intron	N/A	NP_006237.1
	PPP2R5E	NM_001282179.3		c.355-12482G>A		intron	N/A	NP_001269108.1
	PPP2R5E	NM_001282180.3		c.355-12482G>A		intron	N/A	NP_001269109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.355-12482G>A		intron	N/A	ENSP00000337641.3
	PPP2R5E	ENST00000555899.1	TSL:1	c.355-12482G>A		intron	N/A	ENSP00000452396.1
	PPP2R5E	ENST00000553266.5	TSL:1	n.741-12482G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65660 AN: 151884 Hom.: 18490 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.433 AC: 65758 AN: 152002 Hom.: 18546 Cov.: 32 AF XY: 0.429 AC XY: 31855 AN XY: 74310

African (AFR) AF: 0.810 AC: 33574 AN: 41444

American (AMR) AF: 0.273 AC: 4169 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2197 AN: 5158

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4824

European-Finnish (FIN) AF: 0.301 AC: 3171 AN: 10548

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19076 AN: 67970

Other (OTH) AF: 0.393 AC: 827 AN: 2102

Alfa AF: 0.309 Hom.: 11305

Bravo AF: 0.443

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.039
DANN	Benign	0.51
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10140679; hg19: chr14-63901294;