Submissions for variant NM_000081.4(LYST):c.8272G>A (p.Ala2758Thr)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001226282	SCV001398590	uncertain significance	Chédiak-Higashi syndrome	2022-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2758 of the LYST protein (p.Ala2758Thr). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 953917). 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 threonine 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.
Ambry Genetics	RCV004639508	SCV005130183	uncertain significance	Inborn genetic diseases	2024-06-04	criteria provided, single submitter	clinical testing	The c.8272G>A (p.A2758T) alteration is located in exon 31 (coding exon 29) of the LYST gene. This alteration results from a G to A substitution at nucleotide position 8272, causing the alanine (A) at amino acid position 2758 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782676	SCV005394876	uncertain significance	not specified	2024-09-23	criteria provided, single submitter	clinical testing	Variant summary: LYST c.8272G>A (p.Ala2758Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251326 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8272G>A in individuals affected with Chediak-Higashi Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 953917). Based on the evidence outlined above, the variant was classified as uncertain significance.