Submissions for variant NM_000268.4(NF2):c.1113C>T (p.Asn371=)

gnomAD frequency: 0.00033  dbSNP: rs142459414

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000232452	SCV000284539	benign	Neurofibromatosis, type 2	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000232452	SCV000437752	likely benign	Neurofibromatosis, type 2	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Ambry Genetics	RCV000564489	SCV000674125	benign	Hereditary cancer-predisposing syndrome	2017-03-15	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	RCV000586100	SCV000696413	benign	not provided	2016-05-13	criteria provided, single submitter	clinical testing	Variant summary: The NF2 c.1113C>T (p.Asn371Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts changes of binding motifs for RNA splicing enhancers. This variant was found in 112/121300 control chromosomes at a frequency of 0.0009233, which is approximately 49 times the estimated maximal expected allele frequency of a pathogenic NF2 variant (0.0000189), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Genome-Nilou Lab	RCV000232452	SCV002044925	benign	Neurofibromatosis, type 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000564489	SCV002528165	benign	Hereditary cancer-predisposing syndrome	2021-04-14	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000586100	SCV004011392	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	NF2: BP4, BP7, BS1
Color Diagnostics, LLC DBA Color Health	RCV000232452	SCV004357037	benign	Neurofibromatosis, type 2	2022-09-30	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000232452	SCV004821016	benign	Neurofibromatosis, type 2	2024-01-11	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000586100	SCV001926654	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586100	SCV001967813	likely benign	not provided		no assertion criteria provided	clinical testing