Submissions for variant NM_001042492.3(NF1):c.2022C>T (p.Ser674=)

gnomAD frequency: 0.00908  dbSNP: rs2230851

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130488	SCV000185357	benign	Hereditary cancer-predisposing syndrome	2014-06-30	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae	RCV001081129	SCV000262399	benign	Neurofibromatosis, type 1	2024-02-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218285	SCV000269448	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	Ser674Ser in exon 18 of NF1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 2.6% (113/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2230851).
PreventionGenetics, part of Exact Sciences	RCV000218285	SCV000306244	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000680333	SCV000519041	benign	not provided	2016-12-30	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.
Genetic Services Laboratory, University of Chicago	RCV000218285	SCV000595970	benign	not specified	2018-05-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000680333	SCV000885831	benign	not provided	2017-12-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000218285	SCV000919870	benign	not specified	2017-10-23	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.2022C>T (p.Ser674Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 757/250454 control chromosomes (gnomAD) at a frequency of 0.0030225, which is approximately 15 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Athena Diagnostics Inc	RCV000680333	SCV001144738	benign	not provided	2019-06-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001081129	SCV001479293	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130488	SCV002527441	benign	Hereditary cancer-predisposing syndrome	2020-04-17	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV001081129	SCV002561577	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483263	SCV002799024	likely benign	Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis	2021-11-17	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315893	SCV004016413	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000218285	SCV001809337	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000218285	SCV001972698	benign	not specified		no assertion criteria provided	clinical testing