ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7595C>T (p.Ala2532Val)

gnomAD frequency: 0.00066  dbSNP: rs148154172
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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130730 SCV000185621 likely benign Hereditary cancer-predisposing syndrome 2015-12-03 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Other data supporting benign classification
Labcorp Genetics (formerly Invitae), Labcorp RCV000989823 SCV000253228 benign Neurofibromatosis, type 1 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV000034590 SCV000570150 benign not provided 2018-02-05 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.
PreventionGenetics, part of Exact Sciences RCV000480111 SCV000806319 benign not specified 2015-09-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000480111 SCV000917888 benign not specified 2023-01-30 criteria provided, single submitter clinical testing Variant summary: NF1 c.7532C>T (p.Ala2511Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00079 in 251060 control chromosomes. The observed variant frequency is approximately 317-fold of the estimated maximal expected allele frequency for a pathogenic variant in NF1 causing Noonan Syndrome And Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. c.7532C>T has been reported in the literature in individuals affected Neurofibromatosis Type I (e.g. Tsipi_2018, Ben Aim_2019). These report(s) do not provide unequivocal conclusions about association of the variant with NF1-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Fifteen ClinVar submitters (evaluation after 2014) cites the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000480111 SCV000967009 benign not specified 2018-04-06 criteria provided, single submitter clinical testing p.Ala2532Val in exon 51 of NF1: This variant is classified as benign because it has been identified in 0.93% (94/10136) of Ashkenazi Jewish chromosomes by the G enome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs14 8154172). ACMG/AMP Criteria applied (Richards 2015): BA1.
Mendelics RCV000989823 SCV001140397 likely benign Neurofibromatosis, type 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001122667 SCV001281412 benign Neurofibromatosis-Noonan syndrome 2017-04-28 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina RCV000989823 SCV001281413 likely benign Neurofibromatosis, type 1 2017-04-28 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 RCV001122668 SCV001281414 likely benign Café-au-lait macules with pulmonary stenosis 2017-04-28 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 RCV001122669 SCV001281415 likely benign Neurofibromatosis, familial spinal 2017-04-28 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.
Genetic Services Laboratory, University of Chicago RCV000480111 SCV002068160 benign not specified 2019-11-13 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000130730 SCV002528114 benign Hereditary cancer-predisposing syndrome 2020-07-21 criteria provided, single submitter curation
Genome-Nilou Lab RCV000989823 SCV002561307 benign Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000989823 SCV002567771 benign Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002390138 SCV002670768 benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-04-22 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000480111 SCV002774042 benign not specified 2021-04-21 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000130730 SCV002819210 likely benign Hereditary cancer-predisposing syndrome 2022-10-18 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000034590 SCV004142572 likely benign not provided 2024-05-01 criteria provided, single submitter clinical testing NF1: PP3, BS1
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000034590 SCV000043394 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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