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GeneBe

14-63384503-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_006246.5(PPP2R5E):c.1143C>T(p.Asn381=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,613,792 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 53 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 42 hom. )

Consequence

PPP2R5E
NM_006246.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0600
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 -13 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=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-63384503-G-A is Benign according to our data. Variant chr14-63384503-G-A is described in ClinVar as [Benign]. Clinvar id is 768658.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=0.06 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2147/152164) while in subpopulation AFR AF= 0.0491 (2036/41492). AF 95% confidence interval is 0.0473. There are 53 homozygotes in gnomad4. There are 1030 alleles in male gnomad4 subpopulation. Median coverage is 32. 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 2139 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP2R5ENM_006246.5 linkuse as main transcriptc.1143C>T p.Asn381= synonymous_variant 12/14 ENST00000337537.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP2R5EENST00000337537.8 linkuse as main transcriptc.1143C>T p.Asn381= synonymous_variant 12/141 NM_006246.5 P1Q16537-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0141
AC:
2139
AN:
152046
Hom.:
51
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0489
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00504
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0124
GnomAD3 exomes
AF:
0.00357
AC:
897
AN:
251336
Hom.:
24
AF XY:
0.00271
AC XY:
368
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.0492
Gnomad AMR exome
AF:
0.00234
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00137
AC:
2004
AN:
1461628
Hom.:
42
Cov.:
30
AF XY:
0.00114
AC XY:
826
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0486
Gnomad4 AMR exome
AF:
0.00271
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000666
Gnomad4 OTH exome
AF:
0.00285
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0141
AC:
2147
AN:
152164
Hom.:
53
Cov.:
32
AF XY:
0.0138
AC XY:
1030
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0491
Gnomad4 AMR
AF:
0.00497
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.00750
Hom.:
14
Bravo
AF:
0.0157
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 testingInvitaeDec 04, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
8.2
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs61732995; hg19: chr14-63851221; API