Submissions for variant NM_020919.4(ALS2):c.2479A>T (p.Thr827Ser)

gnomAD frequency: 0.00061  dbSNP: rs202219507

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000328276	SCV000426313	uncertain significance	Amyotrophic lateral sclerosis type 2, juvenile	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000382737	SCV000426314	uncertain significance	ALS2-related disorder	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000813075	SCV000953412	likely benign	Infantile-onset ascending hereditary spastic paralysis	2024-01-03	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001289224	SCV001476901	benign	not specified	2019-12-23	criteria provided, single submitter	clinical testing
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino	RCV001358657	SCV001548556	uncertain significance	Tip-toe gait	2021-02-02	criteria provided, single submitter	clinical testing	Gait disorder
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848678	SCV002104728	uncertain significance	Hereditary spastic paraplegia	2018-01-01	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414980	SCV000492876	likely pathogenic	Peripheral axonal neuropathy	2015-03-12	flagged submission	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000328276	SCV001369448	likely pathogenic	Amyotrophic lateral sclerosis type 2, juvenile	2016-01-01	flagged submission	clinical testing	This variant was classified as: Likely pathogenic.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580056	SCV001809512	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001580056	SCV001971088	likely benign	not provided		no assertion criteria provided	clinical testing