Submissions for variant NM_004304.5(ALK):c.2535T>C (p.Gly845=)

gnomAD frequency: 0.63034  dbSNP: rs2256740

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000247134	SCV000310071	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000599942	SCV000429945	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	RCV000247134	SCV000518934	benign	not specified	2016-03-03	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.
Ambry Genetics	RCV000562370	SCV000664934	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	RCV000588051	SCV000698286	benign	not provided	2016-04-27	criteria provided, single submitter	clinical testing	Variant summary: The c.2535T>C variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 4/5 in silico tools via Alamut predict no significant effect on splicing. The variant was observed in the large, broad control population, ExAC with an allele frequency of 61% which includes 24,282 homozygous occurrences, strong evidence that this is a common benign polymorphism. Due to the synonymous nature of this variant and the high allele frequency in the general population, this variant has been classified as Benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000599942	SCV000744255	benign	Neuroblastoma, susceptibility to, 3	2015-09-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000599942	SCV001472434	benign	Neuroblastoma, susceptibility to, 3	2023-11-30	criteria provided, single submitter	clinical testing
Invitae	RCV000599942	SCV001733362	benign	Neuroblastoma, susceptibility to, 3	2024-02-01	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000599942	SCV004017291	benign	Neuroblastoma, susceptibility to, 3	2023-07-07	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000599942	SCV000734190	benign	Neuroblastoma, susceptibility to, 3		no assertion criteria provided	clinical testing