Submissions for variant NM_004304.5(ALK):c.3102G>A (p.Ser1034=)

gnomAD frequency: 0.00029  dbSNP: rs138771319

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000476787	SCV000554731	likely benign	Neuroblastoma, susceptibility to, 3	2024-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000476787	SCV001304211	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.
GeneDx	RCV001591108	SCV001827136	likely benign	not provided	2019-07-25	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256279	SCV002528458	benign	Hereditary cancer-predisposing syndrome	2021-04-23	criteria provided, single submitter	curation
Ambry Genetics	RCV002256279	SCV002607802	likely benign	Hereditary cancer-predisposing syndrome	2022-02-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000476787	SCV003800543	likely benign	Neuroblastoma, susceptibility to, 3	2022-07-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003942510	SCV004758646	likely benign	ALK-related condition	2019-11-20	criteria provided, single submitter	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).