Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000279925 | SCV000435535 | likely benign | Alzheimer disease | 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. |
| Labcorp Genetics |
RCV000279925 | SCV002948154 | benign | Alzheimer disease | 2023-12-06 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479101 | SCV004223213 | likely benign | not specified | 2023-11-28 | criteria provided, single submitter | clinical testing | Variant summary: APP c.225+14G>A alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00019 in 282840 control chromosomes. To our knowledge, no occurrence of c.225+14G>A in individuals affected with Alzheimer Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, classifying the variant as benign (n=1) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |