ClinVar Miner

Submissions for variant NM_000433.3(NCF2):c.563G>A (p.Arg188Lys) (rs115365142)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001088101 SCV000351765 likely benign Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 2 2018-01-12 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV000766500 SCV000513867 uncertain significance not provided 2016-07-26 criteria provided, single submitter clinical testing The R188K variant in the NCF2 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The NHLBI Exome Sequencing Project reports R188K was observed in 39/4406 alleles from individuals of African American background. The R188K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in nearby residue (R184P) has been reported in the Human Gene Mutation Database in association with chronic granulomatous disease (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available evidence, it is unclear whether this variant is a pathogenic variant or a rare benign variant. We consider it to be a variant of uncertain significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000437670 SCV000862527 likely benign not specified 2018-07-19 criteria provided, single submitter clinical testing
Invitae RCV001088101 SCV001122603 benign Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 2 2020-09-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV001088101 SCV001527295 uncertain significance Chronic granulomatous disease, autosomal recessive cytochrome b-positive, type 2 2018-09-14 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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