NM_006246.5:c.157+26239C>A

Variant names:

• chr14-63513290-G-T
• rs4902233
• NM_006246.5:c.157+26239C>A

Variant summary

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

The NM_006246.5(PPP2R5E):​c.157+26239C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,056 control chromosomes in the GnomAD database, including 933 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 0.11 (933 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.148 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	NM_006246.5	MANE Select	c.157+26239C>A		intron	N/A	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.157+26239C>A		intron	N/A	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.157+26239C>A		intron	N/A	NP_001269109.1	Q16537-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.157+26239C>A		intron	N/A	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.157+26239C>A		intron	N/A	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.740+26239C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16330 AN: 151938 Hom.: 934 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.108 AC: 16348 AN: 152056 Hom.: 933 Cov.: 32 AF XY: 0.108 AC XY: 8064 AN XY: 74328

African (AFR) AF: 0.131 AC: 5446 AN: 41458

American (AMR) AF: 0.0796 AC: 1216 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.156 AC: 807 AN: 5158

South Asian (SAS) AF: 0.103 AC: 496 AN: 4820

European-Finnish (FIN) AF: 0.107 AC: 1131 AN: 10580

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0946 AC: 6431 AN: 67982

Other (OTH) AF: 0.114 AC: 240 AN: 2114

Alfa AF: 0.0839 Hom.: 216

Bravo AF: 0.106

Asia WGS AF: 0.145 AC: 504 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	0.36
DANN	Benign	0.45
PhyloP100		-0.43
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: rs4902233; hg19: chr14-63980008;