Submissions for variant NM_000081.4(LYST):c.7870C>T (p.Arg2624Trp)

gnomAD frequency: 0.00280  dbSNP: rs150306354

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001079296	SCV000623917	likely benign	Chédiak-Higashi syndrome	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000606910	SCV000725985	likely benign	not specified	2018-01-03	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Center for Human Genetics Tuebingen	RCV000540467	SCV001147720	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	LYST: BS1
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001079296	SCV001468426	uncertain significance	Chédiak-Higashi syndrome	2021-03-30	criteria provided, single submitter	clinical testing	LYST NM_000081.3 exon 29 p.Arg2624Trp (c.7870C>T): This variant has been reported in the literature in 1 individual with Hemophagocytic Lymphohistiocytosis (HLH) (Mukda 2017 PMID:28353193). However, this variant is present in 0.5% (142/25120) of Finnish alleles, including 1 homozygote, in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-235909738-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:454488). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Genetic Services Laboratory, University of Chicago	RCV000606910	SCV002065508	likely benign	not specified	2018-02-27	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263731	SCV002543664	likely benign	Autoinflammatory syndrome	2022-04-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935392	SCV004754859	likely benign	LYST-related disorder	2019-07-03	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).