chr14-63386534-A-C

Position:

• chr14-63386534-A-C

Variant summary

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

The NM_006246.5(PPP2R5E):​c.1075-1963T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,094 control chromosomes in the GnomAD database, including 4,411 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 0.20 (4411 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16

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 (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.1075-1963T>G		intron_variant		ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.1075-1963T>G		intron_variant		1	NM_006246.5	ENSP00000337641	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29855 AN: 151976 Hom.: 4389 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.197 AC: 29920 AN: 152094 Hom.: 4411 Cov.: 32 AF XY: 0.198 AC XY: 14704 AN XY: 74372

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0912 Hom.: 206

Bravo AF: 0.211

Asia WGS AF: 0.325 AC: 1131 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	0.011
DANN	Benign	0.54

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: rs7146445; hg19: chr14-63853252;