NM_006246.5:c.457-3034C>T

Variant names:

• chr14-63418266-G-A
• rs1951210
• NM_006246.5:c.457-3034C>T

Variant summary

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

The NM_006246.5(PPP2R5E):​c.457-3034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,004 control chromosomes in the GnomAD database, including 3,728 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 0.17 (3728 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006246.5. 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.457-3034C>T		intron	N/A	NP_006237.1
	PPP2R5E	NM_001282179.3		c.457-3034C>T		intron	N/A	NP_001269108.1
	PPP2R5E	NM_001282180.3		c.457-3034C>T		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.457-3034C>T		intron	N/A	ENSP00000337641.3
	PPP2R5E	ENST00000555899.1	TSL:1	c.457-3034C>T		intron	N/A	ENSP00000452396.1
	PPP2R5E	ENST00000553266.5	TSL:1	n.843-3034C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26104 AN: 151886 Hom.: 3719 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.172 AC: 26146 AN: 152004 Hom.: 3728 Cov.: 32 AF XY: 0.170 AC XY: 12659 AN XY: 74288

African (AFR) AF: 0.386 AC: 15975 AN: 41436

American (AMR) AF: 0.102 AC: 1559 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3466

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5164

South Asian (SAS) AF: 0.0492 AC: 237 AN: 4820

European-Finnish (FIN) AF: 0.0982 AC: 1036 AN: 10548

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5365 AN: 67980

Other (OTH) AF: 0.137 AC: 288 AN: 2108

Alfa AF: 0.0984 Hom.: 1994

Bravo AF: 0.184

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.32
PhyloP100		0.27
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: rs1951210; hg19: chr14-63884984;