ClinVar Miner

Submissions for variant NM_002449.5(MSX2):c.286G>T (p.Val96Leu)

gnomAD frequency: 0.00006  dbSNP: rs769329948
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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 RCV001152974 SCV001314217 likely benign Craniosynostosis 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 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.
Illumina Laboratory Services, Illumina RCV001152975 SCV001314218 uncertain significance Parietal foramina 1 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.
Genetic Services Laboratory, University of Chicago RCV001819860 SCV002067203 uncertain significance not specified 2018-07-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002032410 SCV002315390 uncertain significance Cranium bifidum occultum 2023-09-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 96 of the MSX2 protein (p.Val96Leu). This variant is present in population databases (rs769329948, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MSX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 904830). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSX2 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.

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