ClinVar Miner

Submissions for variant NM_000067.3(CA2):c.677G>A (p.Arg226His)

gnomAD frequency: 0.00009  dbSNP: rs201928238
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179708 SCV000231999 uncertain significance not provided 2015-03-17 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001159040 SCV001320723 uncertain significance Osteopetrosis with renal tubular acidosis 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000179708 SCV001995859 uncertain significance not provided 2019-09-24 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV001159040 SCV002775450 uncertain significance Osteopetrosis with renal tubular acidosis 2022-05-26 criteria provided, single submitter clinical testing
Invitae RCV000179708 SCV003255772 uncertain significance not provided 2022-05-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 226 of the CA2 protein (p.Arg226His). This variant is present in population databases (rs201928238, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 198387). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002517756 SCV003756810 uncertain significance Inborn genetic diseases 2022-05-04 criteria provided, single submitter clinical testing The c.677G>A (p.R226H) alteration is located in exon 7 (coding exon 7) of the CA2 gene. This alteration results from a G to A substitution at nucleotide position 677, causing the arginine (R) at amino acid position 226 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.