Submissions for variant NM_000268.4(NF2):c.*4G>A

gnomAD frequency: 0.00165  dbSNP: rs141099051

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000321729	SCV000437757	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.
Ambry Genetics	RCV000574887	SCV000674127	benign	Hereditary cancer-predisposing syndrome	2017-02-10	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589011	SCV000696412	benign	not provided	2016-05-13	criteria provided, single submitter	clinical testing	Variant summary: The NF2 c.*4G>A variant involves the alteration of a non-conserved nucleotide located in the 3'UTR. This variant was found in the large, broad control population, ExAC, with an allele frequency of 95/105096 (1/1106, 0.0009039), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic NF2 variant of 1/52910 (0.0000189), suggesting this variant is likely a benign polymorphism. Therefore, the variant of interest is classified as Benign.
GeneDx	RCV000589011	SCV001778597	likely benign	not provided	2022-05-04	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Genome-Nilou Lab	RCV000321729	SCV002044929	benign	Neurofibromatosis, type 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589011	SCV004042145	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	NF2: BS1, BS2
Color Diagnostics, LLC DBA Color Health	RCV000321729	SCV004357044	benign	Neurofibromatosis, type 2	2022-11-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000321729	SCV004823346	benign	Neurofibromatosis, type 2	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589011	SCV005210293	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003932371	SCV004751223	benign	NF2-related disorder	2021-08-23	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).