ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.21961G>A (p.Asp7321Asn) (rs35625617)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000117743 SCV000269419 benign not specified 2015-01-13 criteria provided, single submitter clinical testing p.Asp7321Asn in exon 149 of NEB: This variant is not expected to have clinical s ignificance because it has been identified in 2.4% (196/8230) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs35625617).
PreventionGenetics,PreventionGenetics RCV000117743 SCV000307302 benign not specified 2016-02-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000554299 SCV000416845 benign Nemaline myopathy 2 2018-01-13 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 RCV000117743 SCV000522736 benign not specified 2016-01-27 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.
Invitae RCV000554299 SCV000640697 benign Nemaline myopathy 2 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000117743 SCV001338305 benign not specified 2020-02-15 criteria provided, single submitter clinical testing Variant summary: NEB c.21961G>A (p.Asp7321Asn) results in a 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 0.016 in 221556 control chromosomes in the gnomAD database, including 40 homozygotes. The observed variant frequency is approximately 4.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in NEB causing Nemaline Myopathy 2 phenotype (0.0035), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.21961G>A in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=4)/likely benign(n=1). Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory,University of Chicago RCV000117743 SCV000151996 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

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