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NM_005188.4(CBL):c.1096-1G>C AND Noonan syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 6, 2012
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:
RCV000038346.5

Allele description [Variation Report for NM_005188.4(CBL):c.1096-1G>C]

NM_005188.4(CBL):c.1096-1G>C

Gene:
CBL:Cbl proto-oncogene [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.3
Genomic location:
Preferred name:
NM_005188.4(CBL):c.1096-1G>C
Other names:
NM_005188.4:c.1096-1G>C
HGVS:
  • NC_000011.10:g.119278165G>C
  • NG_016808.1:g.76886G>C
  • NM_005188.4:c.1096-1G>CMANE SELECT
  • LRG_608t1:c.1096-1G>C
  • LRG_608:g.76886G>C
  • NC_000011.9:g.119148875G>C
  • NM_005188.2:c.1096-1G>C
  • NM_005188.3:c.1096-1G>C
  • c.1096-1G>C
Links:
dbSNP: rs397517076
NCBI 1000 Genomes Browser:
rs397517076
Molecular consequence:
  • NM_005188.4:c.1096-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
Observations:
1

Condition(s)

Name:
Noonan syndrome (NS)
Synonyms:
Noonan's syndrome
Identifiers:
MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000062018Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Dec 6, 2012) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia.

Niemeyer CM, Kang MW, Shin DH, Furlan I, Erlacher M, Bunin NJ, Bunda S, Finklestein JZ, Gorr TA, Mehta P, Schmid I, Kropshofer G, Corbacioglu S, Lang PJ, Klein C, Schlegel PG, Heinzmann A, Schneider M, Starý J, van den Heuvel-Eibrink MM, Hasle H, Locatelli F, et al.

Nat Genet. 2010 Sep;42(9):794-800. doi: 10.1038/ng.641. Epub 2010 Aug 8.

PubMed [citation]
PMID:
20694012
PMCID:
PMC4297285

Mutations in CBL occur frequently in juvenile myelomonocytic leukemia.

Loh ML, Sakai DS, Flotho C, Kang M, Fliegauf M, Archambeault S, Mullighan CG, Chen L, Bergstraesser E, Bueso-Ramos CE, Emanuel PD, Hasle H, Issa JP, van den Heuvel-Eibrink MM, Locatelli F, Stary J, Trebo M, Wlodarski M, Zecca M, Shannon KM, Niemeyer CM.

Blood. 2009 Aug 27;114(9):1859-63. doi: 10.1182/blood-2009-01-198416. Epub 2009 Jul 1.

PubMed [citation]
PMID:
19571318
PMCID:
PMC2738571
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000062018.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The 1096-1G>C variant in CBL has been reported in one individual with clinical f eatures of Noonan syndrome and juvenile myelomonocytic leukemia (JMML; Loh 2009, Niemeyer 2010). This variant was reported to be homozygous in a blood sample an d heterozygous in the germline. Studies have shown that the 1096-1G>A variant i mpacts splicing (Niemeyer 2010). In addition, this variant was not identified in either parent of this individual and therefore likely occurred de novo, assumin g that non-medical explanations including alternate paternity or undisclosed ado ption have been ruled out. This finding supports that this variant is disease ca using and responsible for Noonan-like syndrome and juvenile myelomonocytic leuke mia in this individual. In summary, this variant meets our criteria to be classi fied as pathogenic (http://pcpgm.partners.org/LMM).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Jan 3, 2026