Submissions for variant NM_020919.4(ALS2):c.3520A>T (p.Lys1174Ter)

dbSNP: rs757972700

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800103	SCV000939803	pathogenic	Infantile-onset ascending hereditary spastic paralysis	2023-06-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys1174*) in the ALS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALS2 are known to be pathogenic (PMID: 11586298, 24315819). This variant is present in population databases (rs757972700, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of ALS2-related disease (PMID: 28600779). ClinVar contains an entry for this variant (Variation ID: 645923). For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Lab, University of California San Francisco	RCV001375960	SCV001572952	pathogenic	Amyotrophic lateral sclerosis type 2, juvenile	2019-03-28	criteria provided, single submitter	clinical testing
GeneDx	RCV002051896	SCV002319094	pathogenic	not provided	2022-02-08	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28600779)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001375960	SCV005016584	pathogenic	Amyotrophic lateral sclerosis type 2, juvenile	2024-03-14	criteria provided, single submitter	clinical testing