ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.8644G>A (p.Asp2882Asn) (rs200729207)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723735 SCV000231857 uncertain significance not provided 2015-02-05 criteria provided, single submitter clinical testing
GeneDx RCV000723735 SCV000532338 uncertain significance not provided 2018-02-20 criteria provided, single submitter clinical testing The D2882N variant in the NEB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D2882N variant is observed in 97/277026 (0.035%) alleles in large population cohorts (Lek et al., 2016). The D2882N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Most reported pathogenic variants in the NEB gene are truncating/loss-of-function variants (Stenson et al., 2014). We interpret D2882N as a variant of uncertain significance.
Invitae RCV000527825 SCV000640881 uncertain significance Nemaline myopathy 2 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 2882 of the NEB protein (p.Asp2882Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs200729207, ExAC 0.06%) but has not been reported in the literature in individuals with a NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 198308). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It is not expected to cause disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000527825 SCV001290195 uncertain significance Nemaline myopathy 2 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Natera, Inc. RCV000527825 SCV001456994 uncertain significance Nemaline myopathy 2 2020-01-01 no assertion criteria provided clinical testing

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