Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780563 | SCV000917945 | likely pathogenic | Familial cancer of breast | 2017-12-04 | criteria provided, single submitter | clinical testing | Variant summary: The PALB2 c.761C>G (p.Ser254*) variant results in a premature termination codon, predicted to cause a truncated or absent PALB2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.1240C>T/p.Arg414X, c.2167_2168delAT/p.Met723fsX21). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 246198 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. However, c.761C>A/p.Ser254* has been reported as pathogenic by one clinical laboratory. Taken together, this variant is classified as likely pathogenic. |
| Ambry Genetics | RCV001026625 | SCV001189046 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-07-12 | criteria provided, single submitter | clinical testing | The p.S254* pathogenic mutation (also known as c.761C>G), located in coding exon 4 of the PALB2 gene, results from a C to G substitution at nucleotide position 761. This changes the amino acid from a serine to a stop codon within coding exon 4. 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. |
| Labcorp Genetics |
RCV000780563 | SCV003323121 | pathogenic | Familial cancer of breast | 2023-05-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser254*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. 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: 632930). For these reasons, this variant has been classified as Pathogenic. |
| CZECANCA consortium | RCV003128160 | SCV003804362 | pathogenic | Uterine corpus cancer | 2023-02-21 | no assertion criteria provided | clinical testing |