Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471623 | SCV002769028 | likely benign | Intellectual developmental disorder, autosomal dominant 63, with macrocephaly | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene. Null variants and missense within the RhoGEF domain are associated with intellectual developmental disorder with microcephaly (MIM#617061), while gain-of-function missense within the 7th spectrin repeat are associated with intellectual developmental disorder with macrocephaly (PMID: 32109419). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to serine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v3: 2 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD v3 (p.(Gly2305Asp); 220 heterozygotes, 0 homozygotes). (I) 0504 - Same amino acid change has been observed in placental mammals. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0709 - Another missense variant comparable to the one identified in this case has limited previous evidence for being benign. p.(Gly2305Asp) has been classified as likely benign or benign by diagnostic laboratories in ClinVar. (SB) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Ambry Genetics | RCV005301154 | SCV005961121 | uncertain significance | Inborn genetic diseases | 2024-12-23 | criteria provided, single submitter | clinical testing | The c.6913G>A (p.G2305S) alteration is located in exon 48 (coding exon 48) of the TRIO gene. This alteration results from a G to A substitution at nucleotide position 6913, causing the glycine (G) at amino acid position 2305 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |