Genetic Variant PPP2R5E:c.157+27772G>A (chr14-63511757-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006246.5(PPP2R5E):c.157+27772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,964 control chromosomes in the GnomAD database, including 6,414 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 0.24 ( 6414 hom., cov: 31)

Consequence

PPP2R5E
NM_006246.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.658

Publications

3 publications found

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:

ENSG00000305875 (HGNC:):

ENSG00000305875 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006246.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP2R5E	NM_006246.5	MANE Select	c.157+27772G>A	intron	N/A	NP_006237.1	Q16537-1
PPP2R5E	NM_001282179.3		c.157+27772G>A	intron	N/A	NP_001269108.1	Q16537-1
PPP2R5E	NM_001282180.3		c.157+27772G>A	intron	N/A	NP_001269109.1	Q16537-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.157+27772G>A	intron	N/A	ENSP00000337641.3	Q16537-1
PPP2R5E	ENST00000555899.1	TSL:1	c.157+27772G>A	intron	N/A	ENSP00000452396.1	Q16537-2
PPP2R5E	ENST00000553266.5	TSL:1	n.740+27772G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36734

AN:

151846

Hom.:

6394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.0870

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.215

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

GnomAD4 genome

AF:

0.242

AC:

36796

AN:

151964

Hom.:

6414

Cov.:

AF XY:

0.238

AC XY:

17673

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.503

AC:

20820

AN:

41376

American (AMR)

AF:

0.145

AC:

2206

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

653

AN:

3468

East Asian (EAS)

AF:

0.255

AC:

1319

AN:

5166

South Asian (SAS)

AF:

0.147

AC:

709

AN:

4826

European-Finnish (FIN)

AF:

0.126

AC:

1332

AN:

10586

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9174

AN:

67970

Other (OTH)

AF:

0.214

AC:

452

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1214

2428

3641

4855

6069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.159

Hom.:

2379

Bravo

AF:

0.255

Asia WGS

AF:

0.209

AC:

727

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.6

(source)

DANN

Benign

0.85

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over