14-63513290-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.157+26239C>A		intron_variant	Intron 2 of 13	ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.157+26239C>A		intron_variant	Intron 2 of 13	1	NM_006246.5	ENSP00000337641.3
PPP2R5E	ENST00000555899.1	c.157+26239C>A		intron_variant	Intron 2 of 13	1		ENSP00000452396.1
PPP2R5E	ENST00000553266.5	n.740+26239C>A		intron_variant	Intron 2 of 11	1
PPP2R5E	ENST00000556878.1	n.759+26239C>A		intron_variant	Intron 2 of 2	1

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0946

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0623 Hom.: 85

Bravo AF: 0.106

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.36
DANN	Benign	0.45

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: rs4902233; hg19: chr14-63980008;