Submissions for variant NM_001042492.3(NF1):c.528T>A (p.Asp176Glu)

gnomAD frequency: 0.00398  dbSNP: rs112306990

Total submissions: 26

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129680	SCV000184479	benign	Hereditary cancer-predisposing syndrome	2014-07-14	criteria provided, single submitter	clinical testing	Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Does not segregate with disease in family study (genes with incomplete penetrance);Other strong data supporting benign classification
Genetic Services Laboratory, University of Chicago	RCV000121638	SCV000248163	benign	not specified	2016-10-20	criteria provided, single submitter	clinical testing
Invitae	RCV000199175	SCV000252687	benign	Neurofibromatosis, type 1	2024-02-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000121638	SCV000269458	benign	not specified	2015-06-22	criteria provided, single submitter	clinical testing	p.Asp176Glu in exon 5 of NF1: This variant is not expected to have clinical sign ificance because it has been identified in 1% (67/6564) of Finnish chromosomes a nd 0.5% (307/66442) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs112306990).
PreventionGenetics, part of Exact Sciences	RCV000121638	SCV000306277	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000268253	SCV000401689	likely benign	Neurofibromatosis, familial spinal	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000323382	SCV000401690	likely benign	Café-au-lait macules with pulmonary stenosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000199175	SCV000401691	likely benign	Neurofibromatosis, type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000264802	SCV000401692	likely benign	Neurofibromatosis-Noonan syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034585	SCV000510669	benign	not provided	2017-01-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000034585	SCV000521056	benign	not provided	2016-05-24	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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000199175	SCV000781873	uncertain significance	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034585	SCV000885828	benign	not provided	2020-07-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000121638	SCV000917883	benign	not specified	2017-11-27	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.528T>A (p.Asp176Glu) variant involves the alteration of a non-conserved nucleotide and is predicted to be damaging by 3/5 in silico tools. This variant was found in 1021/277004 control chromosomes (gnomAD), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.011683 (301/25764). This frequency is about 56 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. This variant has been reported in several patients with neurofibromatosis type 1, including evidence of lack of cosegregation with disease and co-occurrence with other pathogenic variants in the same gene (Fahsold_2000, Ars_2003, and Nemethova_2013), strongly supporting for the benign outcome. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign. Taken together, this variant is classified as Benign.
Mendelics	RCV000199175	SCV001140338	likely benign	Neurofibromatosis, type 1	2019-05-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000199175	SCV001478991	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000121638	SCV001879399	benign	not specified	2020-09-16	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034585	SCV002011204	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034585	SCV002498262	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	NF1: BS1, BS2
Sema4, Sema4	RCV000129680	SCV002527613	benign	Hereditary cancer-predisposing syndrome	2020-07-15	criteria provided, single submitter	curation
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034585	SCV000043383	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
ITMI	RCV000121638	SCV000085836	not provided	not specified	2013-09-19	no assertion provided	reference population
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000121638	SCV001743315	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000121638	SCV001808697	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000121638	SCV001974058	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000034585	SCV002036569	likely benign	not provided		no assertion criteria provided	clinical testing