Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001180262 | SCV001345142 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-16 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the -1 position of intron 3 of the PALB2 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. A minigene assay has shown that the variant causes skipping of exon 4 and 5 (PMID: 30890586), which is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
Invitae | RCV001875981 | SCV002234507 | pathogenic | Familial cancer of breast | 2022-05-19 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 3 of the PALB2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 921112). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 30890586). For these reasons, this variant has been classified as Pathogenic. |