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GeneBe

14-63389678-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.077 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1396 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP2R5ENM_006246.5 linkuse as main transcriptc.1008A>G p.Gln336= synonymous_variant 11/14 ENST00000337537.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP2R5EENST00000337537.8 linkuse as main transcriptc.1008A>G p.Gln336= synonymous_variant 11/141 NM_006246.5 P1Q16537-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00917
AC:
1396
AN:
152162
Hom.:
15
Cov.:
32
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.:
23
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.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00917
AC:
1396
AN:
152280
Hom.:
15
Cov.:
32
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.:
6
Bravo
AF:
0.00857
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.0119
EpiControl
AF:
0.0127

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 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.

Other links and lift over

dbSNP: rs61756432; hg19: chr14-63856396; COSMIC: COSV61741925; API