Submissions for variant NM_004304.5(ALK):c.3633C>A (p.Thr1211=)

gnomAD frequency: 0.00021  dbSNP: rs144437923

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000473322	SCV000429929	likely benign	Neuroblastoma, susceptibility to, 3	2018-01-12	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473322	SCV000554759	likely benign	Neuroblastoma, susceptibility to, 3	2024-01-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000571332	SCV000672467	likely benign	Hereditary cancer-predisposing syndrome	2017-03-23	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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000473322	SCV000744252	likely benign	Neuroblastoma, susceptibility to, 3	2017-06-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003422312	SCV004144015	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	ALK: BP4, BP7
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000473322	SCV000745624	likely benign	Neuroblastoma, susceptibility to, 3	2016-01-15	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003950159	SCV004768763	likely benign	ALK-related disorder	2020-02-14	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).