NM_005188.4(CBL):c.1552A>G (p.Thr518Ala) AND CBL-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 3, 2022
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:: RCV002254706.4

Allele description [Variation Report for NM_005188.4(CBL):c.1552A>G (p.Thr518Ala)]

NM_005188.4(CBL):c.1552A>G (p.Thr518Ala)

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.1552A>G (p.Thr518Ala)

HGVS:

NC_000011.10:g.119285089A>G
NG_016808.1:g.83810A>G
NM_005188.2:c.1552A>G
NM_005188.4:c.1552A>GMANE SELECT
NP_005179.2:p.Thr518Ala
NP_005179.2:p.Thr518Ala
LRG_608t1:c.1552A>G
LRG_608:g.83810A>G
LRG_608p1:p.Thr518Ala
NC_000011.9:g.119155799A>G
NM_005188.3:c.1552A>G

Protein change:

T518A

Links:

dbSNP: rs377734587

NCBI 1000 Genomes Browser:

rs377734587

Molecular consequence:

NM_005188.4:c.1552A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CBL-related disorder
Synonyms:: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; CBL MUTATION-ASSOCIATED SYNDROME; CBL SYNDROME; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013308; MedGen: C3150803; OMIM: 613563

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002525964	St. Jude Molecular Pathology, St. Jude Children's Research Hospital	criteria provided, single submitter (St. Jude Assertion Criteria 2020)	Uncertain significance (Feb 3, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002525964

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

criteria provided, single submitter

(St. Jude Assertion Criteria 2020)

Uncertain significance
(Feb 3, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV002525964.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The CBL NM_005188.3 (c.1552A>G; p.Thr518Ala) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 ( https://gnomad.broadinstitute.org/variant/11-119155799-A-G ). Seven of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with Noonan syndrome-like disorders. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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