14-63436838-T-C

Position:

• chr14-63436838-T-C

Variant summary

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

The NM_006246.5(PPP2R5E):​c.355-14744A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,164 control chromosomes in the GnomAD database, including 3,499 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 0.18 (3499 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5E	NM_006246.5	c.355-14744A>G		intron_variant		ENST00000337537.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.355-14744A>G		intron_variant		1	NM_006246.5	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27981 AN: 152046 Hom.: 3481 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.184 AC: 28032 AN: 152164 Hom.: 3499 Cov.: 32 AF XY: 0.179 AC XY: 13286 AN XY: 74382

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0995

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.150

Alfa AF: 0.134 Hom.: 1643

Bravo AF: 0.190

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.0
DANN	Benign	0.71

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: rs11846721; hg19: chr14-63903556;