Submissions for variant NM_014822.4(SEC24D):c.2734C>T (p.Arg912Cys)

gnomAD frequency: 0.00028  dbSNP: rs150351420

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001572692	SCV002306604	uncertain significance	not provided	2022-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 912 of the SEC24D protein (p.Arg912Cys). This variant is present in population databases (rs150351420, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SEC24D-related conditions. ClinVar contains an entry for this variant (Variation ID: 1205869). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Fulgent Genetics, Fulgent Genetics	RCV005023202	SCV005658453	uncertain significance	Cole-Carpenter syndrome 2	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001572692	SCV005908563	uncertain significance	not provided	2024-10-14	criteria provided, single submitter	clinical testing	Reported in a patient with cleft lip and palate in published literature (PMID: 37676273); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing; in the absence of RNA/functional studies the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 37676273)
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572692	SCV001797450	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001572692	SCV001964486	uncertain significance	not provided		no assertion criteria provided	clinical testing