Variant 14-63389678-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006246.5(PPP2R5E):c.1008A>G(p.Gln336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,612,280 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 15 hom., cov: 32)

Exomes 𝑓: 0.014 ( 173 hom. )

Consequence

PPP2R5E
NM_006246.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0770

Variant links:

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]

PPP2R5E links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-63389678-T-C is Benign according to our data. Variant chr14-63389678-T-C is described in ClinVar as [Benign]. Clinvar id is 769862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.077 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0138 (20138/1460000) while in subpopulation NFE AF= 0.0158 (17551/1111312). AF 95% confidence interval is 0.0156. There are 173 homozygotes in gnomad4_exome. There are 9797 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1396 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5E	NM_006246.5 linkuse as main transcript	c.1008A>G	p.Gln336=	synonymous_variant	11/14	ENST00000337537.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5E	ENST00000337537.8 linkuse as main transcript	c.1008A>G	p.Gln336=	synonymous_variant	11/14	1	NM_006246.5	P1	Q16537-1

Frequencies

GnomAD3 genomes

AF:

0.00917

AC:

1396

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00881

AC:

2196

AN:

249178

Hom.:

AF XY:

0.00911

AC XY:

1227

AN XY:

134700

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00536

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00576

Gnomad FIN exome

AF:

0.00916

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00775

GnomAD4 exome

AF:

0.0138

AC:

20138

AN:

1460000

Hom.:

173

Cov.:

AF XY:

0.0135

AC XY:

9797

AN XY:

726196

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00601

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00626

Gnomad4 FIN exome

AF:

0.00807

Gnomad4 NFE exome

AF:

0.0158

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.00917

AC:

1396

AN:

152280

Hom.:

Cov.:

AF XY:

0.00885

AC XY:

659

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00289

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.00962

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00857

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.0

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over