14-63389042-C-T

Variant names:

• chr14-63389042-C-T
• rs6573513
• NM_006246.5:c.1074+570G>A

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+570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,888 control chromosomes in the GnomAD database, including 11,503 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 0.28 (11503 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.1074+570G>A		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+570G>A		intron_variant	Intron 11 of 13	1	NM_006246.5	ENSP00000337641.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43069 AN: 151772 Hom.: 11460 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.284 AC: 43169 AN: 151888 Hom.: 11503 Cov.: 32 AF XY: 0.282 AC XY: 20909 AN XY: 74234

African (AFR) AF: 0.689 AC: 28528 AN: 41392

American (AMR) AF: 0.195 AC: 2982 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2744 AN: 5156

South Asian (SAS) AF: 0.169 AC: 813 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1371 AN: 10528

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0848 AC: 5762 AN: 67954

Other (OTH) AF: 0.238 AC: 502 AN: 2110

Alfa AF: 0.150 Hom.: 11455

Bravo AF: 0.311

Asia WGS AF: 0.368 AC: 1279 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	0.058
DANN	Benign	0.70
PhyloP100		-3.0
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: rs6573513; hg19: chr14-63855760;