rs2180493

Variant names:

• chr14-63423622-A-T
• rs2180493
• NM_006246.5:c.355-1528T>A

Variant summary

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

The ENST00000337537.8(PPP2R5E):​c.355-1528T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,218 control chromosomes in the GnomAD database, including 2,878 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 0.16 (2878 hom., cov: 32)
• Consequence: PPP2R5E ENST00000337537.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000337537.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	NM_006246.5	MANE Select	c.355-1528T>A		intron	N/A	NP_006237.1
	PPP2R5E	NM_001282179.3		c.355-1528T>A		intron	N/A	NP_001269108.1
	PPP2R5E	NM_001282180.3		c.355-1528T>A		intron	N/A	NP_001269109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.355-1528T>A		intron	N/A	ENSP00000337641.3
	PPP2R5E	ENST00000555899.1	TSL:1	c.355-1528T>A		intron	N/A	ENSP00000452396.1
	PPP2R5E	ENST00000553266.5	TSL:1	n.741-1528T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24155 AN: 152100 Hom.: 2863 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.159 AC: 24201 AN: 152218 Hom.: 2878 Cov.: 32 AF XY: 0.156 AC XY: 11642 AN XY: 74440

African (AFR) AF: 0.335 AC: 13922 AN: 41506

American (AMR) AF: 0.124 AC: 1897 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 322 AN: 3472

East Asian (EAS) AF: 0.103 AC: 531 AN: 5180

South Asian (SAS) AF: 0.0968 AC: 467 AN: 4826

European-Finnish (FIN) AF: 0.101 AC: 1070 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5547 AN: 68012

Other (OTH) AF: 0.127 AC: 268 AN: 2108

Alfa AF: 0.130 Hom.: 251

Bravo AF: 0.167

Asia WGS AF: 0.145 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		-0.48
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: rs2180493; hg19: chr14-63890340;