Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019951 | SCV001181371 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-04 | criteria provided, single submitter | clinical testing | The c.997+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 11 in the MUTYH gene. This alteration was confirmed in trans by family studies with a second MUTYH alteration (c.1012C>T) in a patient with adenomatous polyposis at age 42 (Ricci MT et al. J. Hum. Genet., 2017 Feb;62:309-315; external communication with corresponding author). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001860966 | SCV002203405 | uncertain significance | Familial adenomatous polyposis 2 | 2022-08-31 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 823586). This variant has been observed in individual(s) with MUTYH-associated polyposis (PMID: 27829682). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 11 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. It affects a nucleotide within the consensus splice site. |
Color Diagnostics, |
RCV001019951 | SCV004358572 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-09 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +5 position of intron 11 of the MUTYH gene. To our knowledge, functional studies have not been reported for this variant. This variant has been reported with a co-occurring pathogenic MUTYH variant in an individual affected with colon polyps (PMID: 27829682). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |