Submissions for variant NM_001042492.3(NF1):c.2851-6_2851-3del

dbSNP: rs1597716256

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000802183	SCV000942001	pathogenic	Neurofibromatosis, type 1	2024-09-17	criteria provided, single submitter	clinical testing	This sequence change falls in intron 21 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 10862084, 27838393; internal data). In at least one individual the variant was observed to be de novo. This variant is also known as IVS16-6del4. ClinVar contains an entry for this variant (Variation ID: 647632). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 22, and produces a non-functional protein and/or introduces a premature termination codon (internal data). For these reasons, this variant has been classified as Pathogenic.
UAB Medical Genomics Laboratory, UAB Medicine	RCV000802183	SCV001167406	pathogenic	Neurofibromatosis, type 1	2020-01-20	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Medical University Innsbruck	RCV000802183	SCV001250658	pathogenic	Neurofibromatosis, type 1	2020-01-20	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000802183	SCV002561809	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002440682	SCV002752734	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2022-11-10	criteria provided, single submitter	clinical testing	The c.2851-6_2851-3delCTTT intronic pathogenic mutation, located in intron 21 of the NF1 gene, results from a deletion of 4 nucleotides within intron 21 of the NF1 gene. The variant has been detected in multiple individuals with neurofibromatosis type 1 (Messiaen LM et al. Hum Mutat, 2000;15:541-55; Calì F et al. Eur J Med Genet, 2017 Feb;60:93-99). RNA studies have demonstrated that this alteration results in skipping of exon 22 (Messiaen LM et al. Hum Mutat, 2000;15:541-55; Wimmer K et al. Hum Mutat, 2020 06;41:1145-1156; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics	RCV002501077	SCV002813204	pathogenic	Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis	2021-09-16	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV000802183	SCV005417514	likely pathogenic	Neurofibromatosis, type 1		criteria provided, single submitter	clinical testing	PM2_Supporting+PS4_Supporting+PP4+PS3
CeGaT Center for Human Genetics Tuebingen	RCV005411570	SCV006078544	pathogenic	not provided	2025-04-01	criteria provided, single submitter	clinical testing	NF1: PVS1, PM2, PS4:Moderate