Early onset or syndromic epilepsy
Gene: KRAS
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Promoted from amber to green as an additional report on a patient with a variant in the KRAS gene who also has seizures (PMID: 17601930).Created: 26 Nov 2018, 4 p.m.
Comment on list classification: Cardiofaciocutaneous syndrome 2 was confirmed on both OMIM and Gene2Phenotype. One report (PMID: 16474405) found one proband with a missense variant in KRAS who had seizures. This is out of a cohort of 6 patients who have different missense variants in KRAS. Another study (PMID: 21871821) found a Japanese proband with a missense mutation in KRAS who have seizures. Both probands with seizures are from different countries; however, there is not enough evidence to promote the gene.Created: 20 Nov 2018, 5:11 p.m.
Comment on mode of pathogenicity: Variants cause gain-of-function effects (PMID: 21871821, 23059812).Created: 20 Nov 2018, 5:03 p.m.
Seizures are a common feature of CFC.Created: 16 Aug 2018, 2:20 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Cardiofaciocutaneous syndrome 2, MIM#615278
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to KRAS.
Source NHS GMS was added to KRAS.
Zornitza Stark: Seizures are a common feature
Gene: kras has been classified as Green List (High Evidence).
Gene: kras has been classified as Green List (High Evidence).
Publications for gene: KRAS were set to 21871821; 23059812; 16474405; 21871821
Gene: kras has been classified as Amber List (Moderate Evidence).
Publications for gene: KRAS were set to
Mode of pathogenicity for gene: KRAS was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for gene: KRAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KRAS were changed from to Cardiofaciocutaneous syndrome 2, 615278
Expert Review Amber was added to KRAS. Panel: Genetic Epilepsy Syndromes
KRAS was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
KRAS was created by Sarah Leigh