Submissions for variant NM_004304.5(ALK):c.4165-6C>T

gnomAD frequency: 0.20768  dbSNP: rs17007646

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000252384	SCV000310075	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000252384	SCV000335368	benign	not specified	2015-09-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000366824	SCV000429926	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.
GeneDx	RCV000252384	SCV000518935	benign	not specified	2016-04-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586724	SCV000698294	benign	not provided	2016-04-27	criteria provided, single submitter	clinical testing	Variant summary: The variant of interest is located at a non-conserved intronic position, not widely known to affect splicing, with 4/5 in silico programs via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 15272/116488 (1/7 including 1465 homozygotes), which exceeds the predicted maximum expected allele frequency for a pathogenic ALK of 1/2500000. The variant of interest, to our knowledge, has not been published in affected individuals. A reputable clinical laboratory cites the variant with a classification of "benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000366824	SCV001733359	benign	Neuroblastoma, susceptibility to, 3	2025-02-04	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000366824	SCV004016630	benign	Neuroblastoma, susceptibility to, 3	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586724	SCV005239176	benign	not provided		criteria provided, single submitter	not provided
Faculté Pluridciplinaire Nador, Université Mohamed Premier	RCV001250945	SCV001250928	uncertain significance	Squamous cell lung carcinoma	2020-05-05	no assertion criteria provided	clinical testing