Submissions for variant NM_001042492.3(NF1):c.7322-17C>T

gnomAD frequency: 0.00744  dbSNP: rs17884859

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204072	SCV000261682	benign	Neurofibromatosis, type 1	2025-02-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000252088	SCV000306294	benign	not specified		criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000417936	SCV000511093	benign	not provided	2017-01-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000417936	SCV000521067	benign	not provided	2017-09-25	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000252088	SCV000539887	benign	not specified	2016-04-25	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, gene associated with neurofibromatosis
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000417936	SCV000604516	benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000252088	SCV001363367	benign	not specified	2019-10-29	criteria provided, single submitter	clinical testing	Variant summary: NF1 c.7259-17C>T 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 0.0024 in 251342 control chromosomes in the gnomAD database, including 7 homozygotes. The observed variant frequency is approximately 960 fold of 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 benign. To our knowledge, no occurrence of c.7259-17C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4	RCV002256120	SCV002528090	benign	Hereditary cancer-predisposing syndrome	2020-04-28	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000204072	SCV002561281	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002478739	SCV002804275	likely benign	Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis	2021-11-09	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316145	SCV004016411	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000417936	SCV004142568	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	NF1: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000417936	SCV005253797	benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000252088	SCV001807848	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000252088	SCV001972901	benign	not specified		no assertion criteria provided	clinical testing