ClinVar Miner

Submissions for variant NM_001098.3(ACO2):c.718G>A (p.Gly240Ser)

gnomAD frequency: 0.00004  dbSNP: rs764138297
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224671 SCV000281051 uncertain significance not provided 2016-02-02 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000224671 SCV001489115 uncertain significance not provided 2023-07-17 criteria provided, single submitter clinical testing This variant is present in population databases (rs764138297, gnomAD 0.03%). 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. 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 ACO2 protein function. ClinVar contains an entry for this variant (Variation ID: 235453). This missense change has been observed in individual(s) with optic atrophy (PMID: 34056600). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 240 of the ACO2 protein (p.Gly240Ser).
GeneDx RCV000224671 SCV004170582 uncertain significance not provided 2021-12-14 criteria provided, single submitter clinical testing Reported as heterozygous in an individual diagnosed at age 32 years with acute vision loss and was also heterozygous in the asymptomatic mother; the patient had head trauma as a child, followed by epilepsy, meningeal syndrome, and diabetes insipidus (PMID: 34056600); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34056600)
Ambry Genetics RCV004020719 SCV004918237 uncertain significance Inborn genetic diseases 2021-07-15 criteria provided, single submitter clinical testing The c.718G>A (p.G240S) alteration is located in exon 6 (coding exon 6) of the ACO2 gene. This alteration results from a G to A substitution at nucleotide position 718, causing the glycine (G) at amino acid position 240 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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