rs6573514

Variant names:

• chr14-63407037-G-A
• rs6573514
• NM_006246.5:c.549+8103C>T

Variant summary

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

The NM_006246.5(PPP2R5E):​c.549+8103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 152,158 control chromosomes in the GnomAD database, including 798 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 0.091 (798 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.549+8103C>T		intron_variant	Intron 5 of 13	ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.549+8103C>T		intron_variant	Intron 5 of 13	1	NM_006246.5	ENSP00000337641.3

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13796 AN: 152040 Hom.: 797 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0908 AC: 13816 AN: 152158 Hom.: 798 Cov.: 32 AF XY: 0.0921 AC XY: 6848 AN XY: 74378

African (AFR) AF: 0.126 AC: 5210 AN: 41512

American (AMR) AF: 0.0481 AC: 736 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4816

European-Finnish (FIN) AF: 0.169 AC: 1783 AN: 10572

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0841 AC: 5720 AN: 68006

Other (OTH) AF: 0.0726 AC: 153 AN: 2108

Alfa AF: 0.102 Hom.: 170

Bravo AF: 0.0824

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.50
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: rs6573514; hg19: chr14-63873755;