Submissions for variant NM_004304.5(ALK):c.2194G>A (p.Asp732Asn)

gnomAD frequency: 0.00003  dbSNP: rs768366852

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000699154	SCV000827852	uncertain significance	Neuroblastoma, susceptibility to, 3	2024-07-12	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 732 of the ALK protein (p.Asp732Asn). This variant is present in population databases (rs768366852, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 576618). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000761178	SCV000891094	uncertain significance	Familial isolated pituitary adenoma	2021-01-25	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000699154	SCV004191716	uncertain significance	Neuroblastoma, susceptibility to, 3	2023-09-04	criteria provided, single submitter	clinical testing