Submissions for variant NM_000268.4(NF2):c.1392G>A (p.Ala464=)

gnomAD frequency: 0.00006  dbSNP: rs375819833

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088155	SCV000563471	likely benign	Neurofibromatosis, type 2	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003883487	SCV001153663	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	NF2: BP4, BP7
Ambry Genetics	RCV001011305	SCV001171609	likely benign	Hereditary cancer-predisposing syndrome	2017-10-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	RCV001088155	SCV001306000	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome-Nilou Lab	RCV001088155	SCV002045411	likely benign	Neurofibromatosis, type 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001011305	SCV002528179	benign	Hereditary cancer-predisposing syndrome	2021-06-16	criteria provided, single submitter	curation
Color Diagnostics, LLC DBA Color Health	RCV001088155	SCV004357040	benign	Neurofibromatosis, type 2	2022-09-16	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001088155	SCV004821915	benign	Neurofibromatosis, type 2	2023-12-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003972802	SCV004792112	likely benign	NF2-related disorder	2021-03-02	no assertion criteria provided	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).