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NM_014225.6(PPP2R1A):c.544C>T (p.Arg182Trp) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 26, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002515220.2

Allele description [Variation Report for NM_014225.6(PPP2R1A):c.544C>T (p.Arg182Trp)]

NM_014225.6(PPP2R1A):c.544C>T (p.Arg182Trp)

Gene:
PPP2R1A:protein phosphatase 2 scaffold subunit Aalpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.41
Genomic location:
Preferred name:
NM_014225.6(PPP2R1A):c.544C>T (p.Arg182Trp)
HGVS:
  • NC_000019.10:g.52212726C>T
  • NG_047068.1:g.27925C>T
  • NM_001363656.2:c.7C>T
  • NM_014225.6:c.544C>TMANE SELECT
  • NP_001350585.1:p.Arg3Trp
  • NP_055040.2:p.Arg182Trp
  • NC_000019.9:g.52715979C>T
  • NM_014225.5:c.544C>T
  • NR_033500.2:n.488C>T
  • P30153:p.Arg182Trp
Protein change:
R182W; ARG182TRP
Links:
UniProtKB: P30153#VAR_074489; OMIM: 605983.0001; dbSNP: rs786205227
NCBI 1000 Genomes Browser:
rs786205227
Molecular consequence:
  • NM_001363656.2:c.7C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014225.6:c.544C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_033500.2:n.488C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003678861Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 26, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.

Houge G, Haesen D, Vissers LE, Mehta S, Parker MJ, Wright M, Vogt J, McKee S, Tolmie JL, Cordeiro N, Kleefstra T, Willemsen MH, Reijnders MR, Berland S, Hayman E, Lahat E, Brilstra EH, van Gassen KL, Zonneveld-Huijssoon E, de Bie CI, Hoischen A, Eichler EE, et al.

J Clin Invest. 2015 Aug 3;125(8):3051-62. doi: 10.1172/JCI79860. Epub 2015 Jul 13.

PubMed [citation]
PMID:
26168268
PMCID:
PMC4623570

The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction.

Lenaerts L, Reynhout S, Verbinnen I, Laumonnier F, Toutain A, Bonnet-Brilhault F, Hoorne Y, Joss S, Chassevent AK, Smith-Hicks C, Loeys B, Joset P, Steindl K, Rauch A, Mehta SG, Chung WK, Devriendt K, Holder SE, Jewett T, Baldwin LM, Wilson WG, Towner S, et al.

Genet Med. 2021 Feb;23(2):352-362. doi: 10.1038/s41436-020-00981-2. Epub 2020 Oct 27.

PubMed [citation]
PMID:
33106617
PMCID:
PMC7862067

Details of each submission

From Ambry Genetics, SCV003678861.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.544C>T (p.R182W) alteration is located in coding exon 5 of the PPP2R1A gene. This alteration results from a C to T substitution at nucleotide position 544, causing the arginine (R) at amino acid position 182 to be replaced by a tryptophan (W). Based on data from the Genome Aggregation Database (gnomAD), the PPP2R1A c.544C>T alteration was not observed, with coverage at this position. This alteration has been reported to occur de novo in multiple unrelated patients with a neurodevelopmental disorder. Common clinical findings include developmental delay, lack of ambulation, hypotonia, anomalies of the corpus callosum, and epilepsy (Houge, 2015; Lenaerts, 2020). The p.R182 amino acid is conserved in available vertebrate species. Functional studies demonstrated in vitro that protein with this alteration had defective interaction and binding to other subunits of the PP2A holoenzyme, impairing the formation of PP2A, and decreasing the phosphatase activity of the enzyme (Houge, 2015; Lenaerts, 2020). The in silico prediction for the p.R182W alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024