ClinVar Miner

Submissions for variant NM_018136.5(ASPM):c.8741T>C (p.Ile2914Thr)

gnomAD frequency: 0.00021  dbSNP: rs200856894
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145220 SCV000192271 uncertain significance Microcephaly 5, primary, autosomal recessive 2013-02-08 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000145220 SCV000352637 uncertain significance Microcephaly 5, primary, autosomal recessive 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 RCV000609920 SCV000726638 likely benign not specified 2018-01-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001857498 SCV002123935 uncertain significance not provided 2022-04-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2914 of the ASPM protein (p.Ile2914Thr). This variant is present in population databases (rs200856894, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of Seckel syndrome (PMID: 23611254). ClinVar contains an entry for this variant (Variation ID: 157899). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002512567 SCV003692211 uncertain significance Inborn genetic diseases 2021-06-25 criteria provided, single submitter clinical testing The c.8741T>C (p.I2914T) alteration is located in exon 18 (coding exon 18) of the ASPM gene. This alteration results from a T to C substitution at nucleotide position 8741, causing the isoleucine (I) at amino acid position 2914 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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