Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803286 | SCV000943149 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change affects codon 301 of the ACD mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ACD protein. This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant is present in population databases (rs571116752, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 648536). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV002534740 | SCV003560999 | uncertain significance | Inborn genetic diseases | 2021-07-01 | criteria provided, single submitter | clinical testing | The c.903G>A (p.T301T) alteration is located in exon 7 (coding exon 7) of the ACD gene. This alteration consists of a G to A substitution at nucleotide position 903. This nucleotide substitution does not change the amino acid at codon 301. However, this change occurs in the last nucleotide of Exon 7 (c.752_903) which makes it likely to have some effect on normal mRNA splicing. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |