Submissions for variant NM_004304.5(ALK):c.-5G>A

gnomAD frequency: 0.01336  dbSNP: rs56270786

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000378658	SCV000429978	likely 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 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	RCV000587242	SCV000518994	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567652	SCV000664978	benign	Hereditary cancer-predisposing syndrome	2016-11-17	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587242	SCV000698300	benign	not provided	2016-08-24	criteria provided, single submitter	clinical testing	Variant summary: The ALK c.-5G>A variant is a 5 UTR variant that involves the alteration of a non-conserved nucleotide in non-coding exon 1. This variant was found in 90/12078 control chromosomes (1 homozygote) at a frequency of 0.0074516, which is approximately 17884 times the estimated maximal expected allele frequency of a pathogenic ALK variant (0.0000004), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000378658	SCV002048151	benign	Neuroblastoma, susceptibility to, 3	2023-10-16	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000378658	SCV004016388	benign	Neuroblastoma, susceptibility to, 3	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587242	SCV005263314	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003972421	SCV004793650	benign	ALK-related disorder	2019-09-13	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).