Variant rs757369209 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PM2PM5PP2BP4_Strong

The ENST00000485511.6(PPP2R5D):c.157C>A(p.Pro53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P53S) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPP2R5D
ENST00000485511.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

PPP2R5D (HGNC:9312): (protein phosphatase 2 regulatory subunit B'delta) The product of 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 a delta isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R5D links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr6-43006514-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 217455.Status of the report is no_assertion_criteria_provided, 0 stars.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PPP2R5D. . Gene score misZ 3.6476 (greater than the threshold 3.09). Trascript score misZ 4.9069 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, Hogue-Janssens syndrome 1.

BP4

Computational evidence support a benign effect (MetaRNN=0.04306993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPP2R5D	NM_006245.4 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	3/16	ENST00000485511.6	NP_006236.1
PPP2R5D	NM_180976.3 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	3/16		NP_851307.1
PPP2R5D	NM_001270476.2 linkuse as main transcript	c.-297C>A		5_prime_UTR_variant	3/16		NP_001257405.1
PPP2R5D	NM_180977.3 linkuse as main transcript	c.28-420C>A		intron_variant			NP_851308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5D	ENST00000485511.6 linkuse as main transcript	c.157C>A	p.Pro53Thr	missense_variant	3/16	1	NM_006245.4	ENSP00000417963	P1	Q14738-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249938

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

0.69

D;D;D;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.099

MutPred

0.21

Loss of catalytic residue at P52 (P = 0.0291);Loss of catalytic residue at P52 (P = 0.0291);.;

MVP

0.23

MPC

1.3

ClinPred

0.025

GERP RS

4.5

Varity_R

0.044

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over