Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000583497 | SCV000691110 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-21 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 2 of the PMS2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, 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 PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Ambry Genetics | RCV000583497 | SCV002673622 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-10-22 | criteria provided, single submitter | clinical testing | The p.Q25* pathogenic mutation (also known as c.73C>T), located in coding exon 2 of the PMS2 gene, results from a C to T substitution at nucleotide position 73. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Victorian Clinical Genetics Services, |
RCV004787998 | SCV005398423 | pathogenic | Lynch syndrome 4 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with mismatch repair cancer syndrome 4 (MIM#619101) and colorectal cancer, hereditary nonpolyposis, type 4 (MIM#614337). (I) 0108 - This gene is associated with both recessive and dominant disease. Individuals with biallelic variants have mismatch repair cancer syndrome, whereas heterozygous individuals have cancer susceptibility (OMIM). (I) 0112 - The monoallelic condition associated with this gene has incomplete penetrance (PMID: 25856668). (I) 0204 - Variant is predicted to result in a truncated protein (premature termination codon (PTC) is located within the first 102 nucleotides of the coding sequence and is predicted to escape nonsense-mediated decay). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. PTC variants located within the first 102 nucleotides have been reported many times as pathogenic, and observed in a heterozygous state individual with various forms of cancer (ClinVar, PMID: 25856668). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic (ClinVar), and observed in a heterozygous state in an individual with constitutional mismatch repair deficiency syndrome who had an additional variant in the MSH6 gene (PMID: 33247381). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |