Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523957 | SCV000619370 | pathogenic | not provided | 2022-04-03 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation, as the last 157 amino acids are replaced with 36 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28549204) |
Mendelics | RCV000987091 | SCV001136289 | likely pathogenic | Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000523957 | SCV003459368 | pathogenic | not provided | 2022-02-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SETD5 protein in which other variant(s) (p.Ser1286Leufs*84 ) have been determined to be pathogenic (PMID: 24680889). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 450756). This variant is also known as c.3848_3849insC. This premature translational stop signal has been observed in individual(s) with non-syndromic intellectual disability (PMID: 28549204). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1286Leufs*37) in the SETD5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 157 amino acid(s) of the SETD5 protein. |
Ambry Genetics | RCV003362814 | SCV004070458 | pathogenic | Inborn genetic diseases | 2023-08-28 | criteria provided, single submitter | clinical testing | The c.3855dupC (p.S1286Lfs*37) alteration, located in exon 23 (coding exon 21) of the SETD5 gene, consists of a duplication of C at position 3855, causing a translational frameshift with a predicted alternate stop codon after 37 amino acids. This alteration occurs at the 3' terminus of the SETD5 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 10% of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in one individual with features consistent with SETD5-related neurodevelopmental disorder (Stur, 2017). Based on the available evidence, this alteration is classified as pathogenic. |
Laboratory of Medical Genetics, |
RCV000987091 | SCV004171089 | pathogenic | Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency | criteria provided, single submitter | clinical testing | ||
Molecular Genetics laboratory, |
RCV000523957 | SCV004031282 | pathogenic | not provided | 2022-01-03 | no assertion criteria provided | clinical testing |