Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001069182 | SCV001234334 | uncertain significance | KBG syndrome | 2024-07-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2371 of the ANKRD11 protein (p.Ala2371Ser). This variant is present in population databases (rs747911603, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ANKRD11-related conditions. ClinVar contains an entry for this variant (Variation ID: 862455). 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 ANKRD11 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. |
Ambry Genetics | RCV002365776 | SCV002662649 | uncertain significance | Inborn genetic diseases | 2020-03-11 | criteria provided, single submitter | clinical testing | The p.A2371S variant (also known as c.7111G>T), located in coding exon 7 of the ANKRD11 gene, results from a G to T substitution at nucleotide position 7111. The alanine at codon 2371 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV001069182 | SCV003818618 | uncertain significance | KBG syndrome | 2020-06-02 | criteria provided, single submitter | clinical testing | |
Clinical Genomics Laboratory, |
RCV001069182 | SCV005045040 | uncertain significance | KBG syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | The ANKRD11 c.7111G>T (p.Ala2371Ser) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by three submitters. This variant is only observed on 1/124,112 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that the variant does not impact ANKRD11 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. |