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Limb disorders

Gene: ABL1

Amber List (moderate evidence)

ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)
EnsemblGeneIds (GRCh38): ENSG00000097007
EnsemblGeneIds (GRCh37): ENSG00000097007
OMIM: 189980, Gene2Phenotype
ABL1 is in 11 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Downgraded to Amber on advice from Genomics England clinical team. Although there are several dactyly phenotypes, they are not very severe / specific. Clinodactyly is very common in the population as a whole and non-specific. Only one case is reported to have 2-3 toe syndactyly. The limb panel would not be the primary route for diagnosis here and would opt for amber on the basis that we need to see the phenotype across other cases first.
Created: 6 Dec 2018, 1:38 p.m.

Rebecca Foulger (Genomics England curator)

Comment on mode of pathogenicity: Both variants reported so far in PMID:28288113 are missense.
Created: 4 Dec 2018, 11:43 a.m.
Comment on list classification: Updated rating from Red to Green: ABL1 was originally added to the TAAD panel by the external reviewer Chris Buxton. The phenotypes reported in PMID:28288113 are appropriate for inclusion on the limb panel (including clinodactyly, arachnodactyly, camptodactylyly) and seen in sufficient cases (>3 families, 2 missense variants) for a diagnostic rating.
Created: 4 Dec 2018, 11:42 a.m.
Digit anomalies were seen in all four families from PMID:28288113: Subject 1 (family 1) had a hindfoot deformity. Subject 2 (family 1) had long fingers and toes. Subject 3 (family 2), had 5th finger clinodactyly bilaterally. Subject 4 (family 3) had clinodactyly of the 5th fingers. Subject 5 (family 3) had arachnodactyly (Spider hands), Subject 6 (family 4) had bilateral camptodactylyly of little fingers and bilateral 2-3 toe syndactyly.
Created: 4 Dec 2018, 11:40 a.m.
Wang et al.,2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. The variant c.734A>G (p.Tyr245Cys) was found to occur de novo in 3 individuals (families 1-2) and in family 3, the variant was seen in the affected father and daughter. Additionally, a de novo c.1066G>A (p.Ala356Thr) variant was identified in a sixth individual (family 4). Functional assays show that both missense variants cause increased phosphorylation, suggesting increased ABL1 kinase activity.
Sources: Literature
Created: 4 Dec 2018, 11:37 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
congential heart disease, skeletal abnormalities and failure to thrive; clinodactyly; syndactyly; arachnodactyly

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • congential heart disease, skeletal abnormalities and failure to thrive
  • clinodactyly
  • syndactyly
  • arachnodactyly
OMIM
189980
Clinvar variants
Variants in ABL1
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Rebecca Foulger: Wang et al.,2017 (PMID:2828811

6 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: abl1 has been classified as Amber List (Moderate Evidence).

4 Dec 2018, Gel status: 3

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for gene: ABL1 was changed from None to Other

4 Dec 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: abl1 has been classified as Green List (High Evidence).

4 Dec 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: ABL1 was added gene: ABL1 was added to Limb disorders. Sources: Literature Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ABL1 were set to 28288113 Phenotypes for gene: ABL1 were set to congential heart disease, skeletal abnormalities and failure to thrive; clinodactyly; syndactyly; arachnodactyly