Submissions for variant NM_004304.5(ALK):c.702T>A (p.Pro234=)

dbSNP: rs2246745

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000249360	SCV000310080	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000611999	SCV000429965	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	RCV000249360	SCV000518932	benign	not specified	2016-03-02	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000249360	SCV000538275	benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Ambry Genetics	RCV000571090	SCV000664936	benign	Hereditary cancer-predisposing syndrome	2016-12-08	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588673	SCV000698301	benign	not provided	2016-04-27	criteria provided, single submitter	clinical testing	Variant summary: The variant of interest causes a synonymous change involving a conserved nucleotide with 5/5 in silico programs via Alamut predicting no significant effect on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 89037/121392 (34225 homozygotes) indicating that the variant of interest is the major allele (allele most commonly observed in the general population). Therefore, the variant of interest is classified as Benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000611999	SCV000744260	benign	Neuroblastoma, susceptibility to, 3	2015-09-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000611999	SCV001472436	benign	Neuroblastoma, susceptibility to, 3	2023-11-29	criteria provided, single submitter	clinical testing
Invitae	RCV000611999	SCV001733364	benign	Neuroblastoma, susceptibility to, 3	2024-02-01	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000611999	SCV004015467	benign	Neuroblastoma, susceptibility to, 3	2023-07-07	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000611999	SCV000734192	benign	Neuroblastoma, susceptibility to, 3		no assertion criteria provided	clinical testing