Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001267714 | SCV001445966 | uncertain significance | Diamond-Blackfan anemia | 2020-11-16 | criteria provided, single submitter | curation | The homozygous c.175+1G>A variant in ZNF699 was identified by our study in 1 individual with Diamond-Blackfan anemia. The variant has not been previously reported in individuals with Diamond-Blackfan anemia but has been identified in 0.003% (1/30612) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs749115647). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. It is of note that loss of function of ZNF699 in an autosomal recessive disease has not yet been established based on the criteria laid out in Tayoun et al., 2018 (PMID: 30192042). Furthermore, although this gene has been reported in association with Diamond-Blackfan anemia, it currently has limited evidence for these associations. In summary, the clinical significance of the c.175+1G>A variant is uncertain. |
Center for Medical Genetics and Molecular Medicine, |
RCV004692382 | SCV004565354 | pathogenic | DEGCAGS syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | ACMG subscores: PVS1, PM2_sup, PM3_sup |