Submissions for variant NM_001042492.3(NF1):c.8151G>A (p.Pro2717=)

gnomAD frequency: 0.00050  dbSNP: rs2285895

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129364	SCV000184128	benign	Hereditary cancer-predisposing syndrome	2014-06-20	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206206	SCV000262470	benign	Neurofibromatosis, type 1	2025-02-04	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000216274	SCV000269465	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	Pro2717Pro in exon 56 of NF1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 5.2% (10/194) of Han Chinese chromosomes from a broad population by the 1000 Genomes Project (http:/ /www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs2285895).
Illumina Laboratory Services, Illumina	RCV000206206	SCV000401809	benign	Neurofibromatosis, type 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000310315	SCV000401810	benign	Neurofibromatosis-Noonan syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000362723	SCV000401811	benign	Neurofibromatosis, familial spinal	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000270629	SCV000401812	benign	Café-au-lait macules with pulmonary stenosis	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000590571	SCV000529378	likely benign	not provided	2020-09-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25480383)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590571	SCV000696410	benign	not provided	2016-05-12	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.8088G>A (p.Pro2696Pro) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools calculating no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 198/119290 (2 homozygotes, 1/602 (frequency: 0.00166), predominantly in the East Asian cohort, 166/8566 (1 homozygote, 1/51, frequency: 0301938), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic NF1 variant of 1/4798 (0.0002084). Therefore, suggesting this variant is a common polymorphism found in population(s) of East Asian origin. In addition, multiple clinical laboratories have cited the variant as "benign." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000216274	SCV000806326	benign	not specified	2016-08-25	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000206206	SCV001478992	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000216274	SCV002068303	benign	not specified	2019-09-09	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000129364	SCV002528142	benign	Hereditary cancer-predisposing syndrome	2020-12-11	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV000206206	SCV002561363	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000362723	SCV004016435	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing