Submissions for variant NM_004304.5(ALK):c.2430C>T (p.Ser810=)

gnomAD frequency: 0.00086  dbSNP: rs150292405

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000459188	SCV000429948	benign	Neuroblastoma, susceptibility to, 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000459188	SCV000554746	benign	Neuroblastoma, susceptibility to, 3	2025-02-04	criteria provided, single submitter	clinical testing
GeneDx	RCV002222490	SCV002499881	likely benign	not provided	2021-06-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256212	SCV002528427	benign	Hereditary cancer-predisposing syndrome	2021-03-04	criteria provided, single submitter	curation
Ambry Genetics	RCV002256212	SCV002735292	likely benign	Hereditary cancer-predisposing syndrome	2022-02-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000459188	SCV004016977	benign	Neuroblastoma, susceptibility to, 3	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003950160	SCV004761523	likely benign	ALK-related disorder	2022-03-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).