ClinVar Miner

Submissions for variant NM_013275.6(ANKRD11):c.5552A>G (p.Tyr1851Cys)

gnomAD frequency: 0.00004  dbSNP: rs376366933
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429101 SCV000525395 uncertain significance not provided 2016-03-09 criteria provided, single submitter clinical testing The Y1851C variant in the ANKRD11 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y1851C variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Y1851C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across mammalian species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Y1851C as a variant of uncertain significance.
Ambry Genetics RCV002348194 SCV002649439 uncertain significance Inborn genetic diseases 2017-06-20 criteria provided, single submitter clinical testing The p.Y1851C variant (also known as c.5552A>G), located in coding exon 7 of the ANKRD11 gene, results from an A to G substitution at nucleotide position 5552. The tyrosine at codon 1851 is replaced by cysteine, an amino acid with some highly dissimilar properties. This amino acid position is not well 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.
Invitae RCV003640892 SCV004530175 uncertain significance KBG syndrome 2023-03-22 criteria provided, single submitter clinical testing 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 ANKRD11 protein function. ClinVar contains an entry for this variant (Variation ID: 384522). This variant has not been reported in the literature in individuals affected with ANKRD11-related conditions. This variant is present in population databases (rs376366933, gnomAD 0.02%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1851 of the ANKRD11 protein (p.Tyr1851Cys).

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