ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.140C>T (p.Ser47Leu)

gnomAD frequency: 0.00001  dbSNP: rs541315214
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000551780 SCV000648608 likely benign Neuroblastoma, susceptibility to, 3 2024-01-08 criteria provided, single submitter clinical testing
GeneDx RCV001356620 SCV003925917 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000551780 SCV004016844 likely benign Neuroblastoma, susceptibility to, 3 2023-07-07 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356620 SCV001551838 likely benign not provided no assertion criteria provided clinical testing The ALK p.S47L variant was not identified in the literature nor was it identified in COSMIC. The variant was identified in dbSNP (ID: rs541315214) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 86 of 270974 chromosomes (2 homozygous) at a frequency of 0.0003174, and was observed at the highest frequency in the South Asian population in 83 of 30386 chromosomes (2 homozygous) (freq: 0.002732) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.S47 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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