ClinVar Miner

Submissions for variant NM_005337.5(NCKAP1L):c.2718G>C (p.Lys906Asn)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003829535 SCV004628385 uncertain significance not provided 2023-01-05 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with NCKAP1L-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 906 of the NCKAP1L protein (p.Lys906Asn).
Neuberg Centre For Genomic Medicine, NCGM RCV004723506 SCV005329416 uncertain significance Immunodeficiency 72 with autoinflammation 2023-05-20 criteria provided, single submitter clinical testing The observed missense variant c.2718G>C (p.Lys906Asn) in NCKAP1L gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Lys906Asn variant is present with an allele frequency of 0.0004% on gnomAD exomes database. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidence (SIFT - damaging; Polyphen - probably damaging; MutationTaster - disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Lys906Asn in NCKAP1L is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Lys at position 906 is changed to a Asn changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).

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