ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6158G>A (p.Arg2053Lys)

dbSNP: rs1060500289
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000457886 SCV000542056 uncertain significance Neurofibromatosis, type 1 2022-02-10 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 404479). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 2032 of the NF1 protein (p.Arg2032Lys).
Ambry Genetics RCV000567130 SCV000662755 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-18 criteria provided, single submitter clinical testing The p.R2053K variant (also known as c.6158G>A), located in coding exon 42 of the NF1 gene, results from a G to A substitution at nucleotide position 6158. The arginine at codon 2053 is replaced by lysine, an amino acid with highly similar properties. 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. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 110000alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive.Since supporting evidence is limited at this time, the clinical significance of this alterationremains unclear.
Genome-Nilou Lab RCV000457886 SCV002560939 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004559065 SCV005047927 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-05-21 criteria provided, single submitter clinical testing The c.6095G>A (p.R2032K) alteration is located in exon 41 (coding exon 41) of the NF1 gene. This alteration results from a G to A substitution at nucleotide position 6095, causing the arginine (R) at amino acid position 2032 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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