Submissions for variant NM_000268.4(NF2):c.246G>A (p.Leu82=)

gnomAD frequency: 0.00021  dbSNP: rs371270318

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000469303	SCV000563482	benign	Neurofibromatosis, type 2	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000563920	SCV000674128	likely benign	Hereditary cancer-predisposing syndrome	2017-04-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000469303	SCV001308954	benign	Neurofibromatosis, type 2	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001534714	SCV001751656	likely benign	not provided	2020-12-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000469303	SCV002044920	benign	Neurofibromatosis, type 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000563920	SCV002528190	benign	Hereditary cancer-predisposing syndrome	2020-12-17	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001534714	SCV004154849	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing	NF2: BP4
PreventionGenetics, part of Exact Sciences	RCV003925394	SCV004742372	likely benign	NF2-related condition	2019-09-13	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).