Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001135552 | SCV001295339 | likely benign | Familial cold autoinflammatory syndrome 2 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Ce |
RCV001200245 | SCV001371150 | uncertain significance | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002558292 | SCV003746360 | uncertain significance | Inborn genetic diseases | 2022-01-27 | criteria provided, single submitter | clinical testing | The c.2120C>T (p.A707V) alteration is located in exon 4 (coding exon 4) of the NLRP12 gene. This alteration results from a C to T substitution at nucleotide position 2120, causing the alanine (A) at amino acid position 707 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Invitae | RCV001135552 | SCV004344854 | uncertain significance | Familial cold autoinflammatory syndrome 2 | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 707 of the NLRP12 protein (p.Ala707Val). This variant is present in population databases (rs202169378, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 894557). 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 valine 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. |