Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002338651 | SCV002641587 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2016-08-23 | criteria provided, single submitter | clinical testing | The c.5205+5_5205+6delGT intronic variant, located in intron 36 of the NF1 gene, results from a deletion of two nucleotides within intron 36 of the NF1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. The deleted nucleotides are well conserved in available vertebrate species. Using the BDGP, ESEfinder, and Human Splicing Finder (HSF) splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. In addition, substitutions of G at the same +5 position have been identified in multiple patients with neurofibromatosis type I and reported to result in in-frame deletion of 18 amino acids due to aberrant splicing (Ars E et al. J. Med. Genet., 2003 Jun;40:e82; Lee MJ et al. Hum. Mutat., 2006 Aug;27:832; Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |