Submissions for variant NM_000081.4(LYST):c.5518T>G (p.Ser1840Ala)

gnomAD frequency: 0.00485  dbSNP: rs115330112

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224027	SCV000280673	likely benign	not provided	2016-05-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000250486	SCV000301974	benign	not specified		criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000250486	SCV000595662	uncertain significance	not specified	2016-11-04	criteria provided, single submitter	clinical testing
Invitae	RCV000546310	SCV000623903	benign	Chédiak-Higashi syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000546310	SCV000743802	likely benign	Chédiak-Higashi syndrome	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000546310	SCV000745218	likely benign	Chédiak-Higashi syndrome	2016-11-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000224027	SCV001147722	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	LYST: BS2
Illumina Laboratory Services, Illumina	RCV000546310	SCV001256525	benign	Chédiak-Higashi syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Johns Hopkins Genomics, Johns Hopkins University	RCV000546310	SCV001431516	likely benign	Chédiak-Higashi syndrome	2020-08-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000224027	SCV001777536	likely benign	not provided	2020-03-19	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262830	SCV002543334	likely benign	Autoinflammatory syndrome	2021-06-25	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000546310	SCV003920175	likely benign	Chédiak-Higashi syndrome	2022-08-23	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.7% (539/68038) including 2 homozygotes (https://gnomad.broadinstitute.org/variant/1-235775029-A-C?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Benign or Likely benign (Variation ID:235239). This variant amino acid Alanine (Ala) is present in multiple species including at least one mammal and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000224027	SCV002035977	likely benign	not provided		no assertion criteria provided	clinical testing