Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000471259 | SCV000554730 | likely benign | Neuroblastoma, susceptibility to, 3 | 2024-01-24 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000471259 | SCV004017044 | likely benign | Neuroblastoma, susceptibility to, 3 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000119988 | SCV000084118 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Department of Pathology and Laboratory Medicine, |
RCV001357328 | SCV001552770 | likely benign | not provided | no assertion criteria provided | clinical testing | The ALK p.E405D variant was not identified in the literature nor was it identified in COSMIC. The variant was identified in dbSNP (ID: rs370235133) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 97 of 282670 chromosomes (2 homozygous) at a frequency of 0.0003432, and was observed at the highest frequency in the South Asian population in 94 of 30614 chromosomes (2 homozygous) (freq: 0.003070) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.E405 residue is conserved in mammals however computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out 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. |