NM_006246.5:c.355-14744A>G

Variant names:

• chr14-63436838-T-C
• rs11846721
• NM_006246.5:c.355-14744A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.94).
• 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 rank	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.355-14744A>G		intron_variant	Intron 3 of 13	ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.355-14744A>G		intron_variant	Intron 3 of 13	1	NM_006246.5	ENSP00000337641.3

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

African (AFR) AF: 0.350 AC: 14536 AN: 41474

American (AMR) AF: 0.112 AC: 1715 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3472

East Asian (EAS) AF: 0.104 AC: 539 AN: 5176

South Asian (SAS) AF: 0.101 AC: 486 AN: 4826

European-Finnish (FIN) AF: 0.0995 AC: 1055 AN: 10604

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8691 AN: 68014

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.141 Hom.: 3003

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
PhyloP100		-0.35
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: rs11846721; hg19: chr14-63903556;