Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001966034 | SCV002237853 | uncertain significance | Duchenne muscular dystrophy | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 45 of the DMD gene. It does not directly change the encoded amino acid sequence of the DMD protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1461798). 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 is not likely to affect RNA splicing. 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 | RCV002361310 | SCV002663468 | uncertain significance | Cardiovascular phenotype | 2021-09-27 | criteria provided, single submitter | clinical testing | The c.6614+4G>A intronic variant results from a G to A substitution 4 nucleotides after coding exon 45 in the DMD gene. This nucleotide position is not well conserved in available vertebrate species. Based on data from gnomAD, the A allele has an overall frequency of <0.01% (1/182774) total alleles studied, with 1 hemizygote observed. The highest observed frequency was <0.01% (1/27341) of Latino/Admixed American alleles. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |