ClinVar Miner

Submissions for variant NM_000081.4(LYST):c.8143G>A (p.Val2715Ile)

gnomAD frequency: 0.00001  dbSNP: rs202010795
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001101818 SCV001258459 uncertain significance Chédiak-Higashi syndrome 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.
Invitae RCV001101818 SCV001499236 uncertain significance Chédiak-Higashi syndrome 2022-08-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2715 of the LYST protein (p.Val2715Ile). This variant is present in population databases (rs202010795, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. ClinVar contains an entry for this variant (Variation ID: 876715). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001772319 SCV002002787 uncertain significance not provided 2021-04-05 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV003353162 SCV004071133 uncertain significance Inborn genetic diseases 2023-07-25 criteria provided, single submitter clinical testing The c.8143G>A (p.V2715I) alteration is located in exon 30 (coding exon 28) of the LYST gene. This alteration results from a G to A substitution at nucleotide position 8143, causing the valine (V) at amino acid position 2715 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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