Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658269 | SCV000780040 | uncertain significance | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in which both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001308472 | SCV001497924 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2023-06-23 | criteria provided, single submitter | clinical testing | 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 create or strengthen a 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. ClinVar contains an entry for this variant (Variation ID: 546400). This sequence change falls in intron 17 of the LRSAM1 gene. It does not directly change the encoded amino acid sequence of the LRSAM1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368570954, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. |
Ambry Genetics | RCV002386130 | SCV002689885 | uncertain significance | Inborn genetic diseases | 2022-05-13 | criteria provided, single submitter | clinical testing | The c.1347+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 16 in the LRSAM1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant Charcot-Marie-Tooth disease, type 2P (CMT2P); however, its contribution to the development of autosomal recessive CMT2P is uncertain. |