NM_006246.5:c.1074+2091T>C

Variant names:

• chr14-63387521-A-G
• rs10135846
• NM_006246.5:c.1074+2091T>C

Variant summary

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

The NM_006246.5(PPP2R5E):​c.1074+2091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,822 control chromosomes in the GnomAD database, including 2,414 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 0.15 (2414 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.1074+2091T>C		intron_variant	Intron 11 of 13	ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.1074+2091T>C		intron_variant	Intron 11 of 13	1	NM_006246.5	ENSP00000337641.3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22936 AN: 151708 Hom.: 2395 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.151 AC: 22994 AN: 151822 Hom.: 2414 Cov.: 32 AF XY: 0.154 AC XY: 11433 AN XY: 74172

African (AFR) AF: 0.245 AC: 10136 AN: 41388

American (AMR) AF: 0.150 AC: 2279 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2475 AN: 5132

South Asian (SAS) AF: 0.163 AC: 780 AN: 4798

European-Finnish (FIN) AF: 0.116 AC: 1223 AN: 10558

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0783 AC: 5316 AN: 67922

Other (OTH) AF: 0.142 AC: 299 AN: 2108

Alfa AF: 0.127 Hom.: 366

Bravo AF: 0.161

Asia WGS AF: 0.314 AC: 1091 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		0.087
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: rs10135846; hg19: chr14-63854239;