Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000473494 | SCV000541431 | pathogenic | Werner syndrome | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg225*) in the WRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 404010). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV000473494 | SCV001950098 | pathogenic | Werner syndrome | 2021-07-13 | criteria provided, single submitter | clinical testing | This variant was identified as compound heterozygous with NM_000553.6:c.3030_3033del. |
Prevention |
RCV003418150 | SCV004107943 | pathogenic | WRN-related disorder | 2023-07-13 | criteria provided, single submitter | clinical testing | The WRN c.673C>T variant is predicted to result in premature protein termination (p.Arg225*). This variant has been reported in the heterozygous state in individuals from an breast cancer exome sequencing cohort and an exome carrier screening cohort (Table S5, Maxwell et al. 2016. PubMed ID: 27153395; Table S1, Capalbo et al. 2019. PubMed ID: 31589614). This variant is reported in 0.0024% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-30925792-C-T). Nonsense variants in WRN are expected to be pathogenic. This variant is interpreted as pathogenic. |
Baylor Genetics | RCV000473494 | SCV004208846 | likely pathogenic | Werner syndrome | 2023-07-03 | criteria provided, single submitter | clinical testing |