Submissions for variant NM_001042492.3(NF1):c.655-2A>C

dbSNP: rs1555608734

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659965	SCV000781877	likely pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000659965	SCV000818700	pathogenic	Neurofibromatosis, type 1	2018-02-28	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 6 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. Different variants affecting this nucleotide (c.655-2A>T and c.655-2A>G) have been reported in individuals affected with neurofibromatosis type 1 and determined to be pathogenic (PMID: 10712197, 27074763). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000659965	SCV001479038	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000659965	SCV002561593	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing