Submissions for variant NM_000026.4(ADSL):c.357+6C>T

gnomAD frequency: 0.00015  dbSNP: rs181628906

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123547	SCV000166886	benign	not specified	2013-03-19	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.
Illumina Laboratory Services, Illumina	RCV000289803	SCV000438675	uncertain significance	Adenylosuccinate lyase deficiency	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	RCV000289803	SCV000547389	likely benign	Adenylosuccinate lyase deficiency	2024-01-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710482	SCV000840713	uncertain significance	not provided	2022-03-29	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000289803	SCV000898518	uncertain significance	Adenylosuccinate lyase deficiency	2021-03-30	criteria provided, single submitter	clinical testing	ADSL NM_000026 exon 2 c.357+6C>T: This variant has not been reported in the literature but is present in 0.3% (39/10152) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs181628906). This variant is present in ClinVar (Variation ID:136308). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.