rs1298412798

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174907.4(PPP4R2):c.118A>G(p.Ile40Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PPP4R2
NM_174907.4 missense, splice_region

Scores

Splicing: ADA: 0.0005342

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Publications

0 publications found

Variant links:

Genes affected

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

PPP4R2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059205085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP4R2	NM_174907.4 link	c.118A>G	p.Ile40Val	missense_variant, splice_region_variant	Exon 3 of 9	ENST00000356692.10	NP_777567.1	Q9NY27-1
PPP4R2	NM_001318026.2 link	c.4A>G	p.Ile2Val	missense_variant, splice_region_variant	Exon 3 of 9		NP_001304955.1	Q9NY27
PPP4R2	NM_001318025.2 link	c.117-11850A>G		intron_variant	Intron 2 of 7		NP_001304954.1	Q9NY27-2
PPP4R2	NM_001318027.2 link	c.-164-11850A>G		intron_variant	Intron 2 of 7		NP_001304956.1	Q9NY27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP4R2	ENST00000356692.10 link	c.118A>G	p.Ile40Val	missense_variant, splice_region_variant	Exon 3 of 9	1	NM_174907.4	ENSP00000349124.5		Q9NY27-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000638

AC:

AN:

156732

AF XY:

0.0000120

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380638

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30496

American (AMR)

AF:

0.00

AC:

AN:

32738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24512

East Asian (EAS)

AF:

0.00

AC:

AN:

35992

South Asian (SAS)

AF:

0.00

AC:

AN:

77420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4462

European-Non Finnish (NFE)

AF:

9.36e-7

AC:

AN:

1067896

Other (OTH)

AF:

0.00

AC:

AN:

57078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.118A>G (p.I40V) alteration is located in exon 3 (coding exon 3) of the PPP4R2 gene. This alteration results from a A to G substitution at nucleotide position 118, causing the isoleucine (I) at amino acid position 40 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0039

T;T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.73

N;.;.

PhyloP100

3.3

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.60

T;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.016

B;.;.

Vest4

0.085

MutPred

0.22

Gain of catalytic residue at I40 (P = 0.0983);Gain of catalytic residue at I40 (P = 0.0983);.;

MVP

0.15

MPC

0.064

ClinPred

0.29

GERP RS

4.3

Varity_R

0.057

gMVP

0.29

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00053

dbscSNV1_RF

Benign

0.028

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over