Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001843856 | SCV002103039 | uncertain significance | Holoprosencephaly 5 | 2022-01-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001843856 | SCV004275237 | uncertain significance | Holoprosencephaly 5 | 2023-04-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1343256). This variant has been observed in individuals with holoprosencephaly (PMID: 19177455, 21940735). 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, c.1377_1406del, results in the deletion of 10 amino acid(s) of the ZIC2 protein (p.Ala461_Ala470del), but otherwise preserves the integrity of the reading frame. This variant disrupts a region of the ZIC2 protein in which other variant(s) (p.Ala461_465del) have been observed in individuals with ZIC2-related conditions (PMID: 19955556). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |