14-63421604-T-C

Position:

• chr14-63421604-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006246.5(PPP2R5E):​c.456+389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,230 control chromosomes in the GnomAD database, including 1,045 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 0.12 (1045 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.456+389A>G		intron_variant		ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.456+389A>G		intron_variant		1	NM_006246.5	ENSP00000337641	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17727 AN: 152112 Hom.: 1041 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.117 AC: 17738 AN: 152230 Hom.: 1045 Cov.: 32 AF XY: 0.114 AC XY: 8487 AN XY: 74434

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0984

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.113 Hom.: 987

Bravo AF: 0.114

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs10145042; hg19: chr14-63888322;