Submissions for variant NM_001042492.3(NF1):c.8113+20G>A

gnomAD frequency: 0.01406  dbSNP: rs55747230

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000254323	SCV000306300	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000680332	SCV000519033	benign	not provided	2016-04-08	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000680332	SCV000604456	benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000254323	SCV001363368	benign	not specified	2019-08-12	criteria provided, single submitter	clinical testing	Variant summary: NF1 c.8050+20G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.013 in 251088 control chromosomes, predominantly at a frequency of 0.019 within the Non-Finnish European subpopulation in the gnomAD database, including 25 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 8000-folds over the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Two ClinVar submissions (evaluation after 2014) cite the varinat as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002057434	SCV002433783	benign	Neurofibromatosis, type 1	2025-02-04	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000254323	SCV002550909	benign	not specified	2022-07-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002057434	SCV002561355	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316373	SCV004016430	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000680332	SCV005253803	benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000254323	SCV001807208	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000254323	SCV001967393	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000254323	SCV001979746	benign	not specified		no assertion criteria provided	clinical testing