ClinVar Miner

Submissions for variant NM_001852.4(COL9A2):c.1732C>G (p.Pro578Ala)

gnomAD frequency: 0.00009  dbSNP: rs528002132
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000365813 SCV000357502 uncertain significance Epiphyseal dysplasia, multiple, 2 2018-01-12 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000419675 SCV000535066 uncertain significance not provided 2024-10-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this missense variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV000419675 SCV002202497 uncertain significance not provided 2024-09-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 578 of the COL9A2 protein (p.Pro578Ala). This variant is present in population databases (rs528002132, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL9A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 297293). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL9A2 protein function with a negative predictive value of 95%. 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 RCV002494923 SCV002780167 uncertain significance Epiphyseal dysplasia, multiple, 2; Stickler syndrome, type 5 2021-07-22 criteria provided, single submitter clinical testing

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