NM_002834.5(PTPN11):c.214G>C (p.Ala72Pro) AND Noonan syndrome 3

Clinical significance:Likely pathogenic (Last evaluated: Jan 30, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000588856.1

Allele description [Variation Report for NM_002834.5(PTPN11):c.214G>C (p.Ala72Pro)]

NM_002834.5(PTPN11):c.214G>C (p.Ala72Pro)

Gene:
PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.13
Genomic location:
Preferred name:
NM_002834.5(PTPN11):c.214G>C (p.Ala72Pro)
Other names:
p.A72P:GCC>CCC
HGVS:
  • NC_000012.12:g.112450394G>C
  • NG_007459.1:g.36663G>C
  • NM_001330437.2:c.214G>C
  • NM_001374625.1:c.211G>C
  • NM_002834.5:c.214G>CMANE SELECT
  • NM_080601.3:c.214G>C
  • NP_001317366.1:p.Ala72Pro
  • NP_001361554.1:p.Ala71Pro
  • NP_002825.3:p.Ala72Pro
  • NP_542168.1:p.Ala72Pro
  • LRG_614t1:c.214G>C
  • LRG_614:g.36663G>C
  • NC_000012.11:g.112888198G>C
  • NM_002834.3:c.214G>C
  • NM_080601.1:c.214G>C
  • c.214G>C
Protein change:
A71P
Links:
dbSNP: rs121918453
NCBI 1000 Genomes Browser:
rs121918453
Molecular consequence:
  • NM_001330437.2:c.214G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.211G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.214G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.214G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Noonan syndrome 3 (NS3)
Synonyms:
KRAS gene related Noonan syndrome
Identifiers:
MONDO: MONDO:0012371; MedGen: C1860991; Orphanet: 648; OMIM: 609942

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000698069Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Jan 30, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

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

Citations

PubMed

PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings.

Lee KA, Williams B, Roza K, Ferguson H, David K, Eddleman K, Stone J, Edelmann L, Richard G, Gelb BD, Kornreich R.

Clin Genet. 2009 Feb;75(2):190-4. doi: 10.1111/j.1399-0004.2008.01085.x. Epub 2008 Aug 26.

PubMed [citation]
PMID:
18759865

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698069.1

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

Description

Variant summary: The PTPN11 c.214G>C (p.Ala72Pro) variant involves the alteration of a conserved nucleotide and is located at SH2 domain of the protein. 4/4 in silico tools predict damaging outcome for this variant. This variant is absent in 121394 control chromosomes from ExAC. PTPN11 p.Ala72Ser variant has been classified as pathogenic for NS phenotype by our laboratory and p.Ala72Thr as possibly pathogenic for JMML/ALL phenotype. Other pathogenic/potentially pathogenic variants at the same residue reported in ClinVar are p.Ala72Gly and p.Ala72Val. Thus, codon p.Ala72 is a mutational hot-spot. This variant has been reported as a germline mutation in two cases with clinical features of Noonans syndrome (Lee_2008, Hakami_2016) and as a somatic mutation in one case with acute monocytic/monoblastic leukemia (Liu_2016). Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic/likely pathogenic. Taken together, this variant is currently classified as likely pathogenic.

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

Last Updated: Sep 23, 2021

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