Submissions for variant NM_001042492.3(NF1):c.6922-14_6922-13del

dbSNP: rs146785663

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243164	SCV000306286	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000680365	SCV000572673	likely benign	not provided	2018-07-05	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000243164	SCV001339023	benign	not specified	2020-03-23	criteria provided, single submitter	clinical testing	Variant summary: NF1 c.6859-14_6859-13delAT 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. 4/4 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 0.00075 in 282828 control chromosomes, predominantly at a frequency of 0.0077 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3080 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 a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.6859-14_6859-13delAT in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000680365	SCV001474290	benign	not provided	2020-10-28	criteria provided, single submitter	clinical testing
Invitae	RCV002057432	SCV002405162	benign	Neurofibromatosis, type 1	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002057432	SCV002561245	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000680365	SCV002585636	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	NF1: BS1