Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000664658 | SCV000788658 | pathogenic | Alstrom syndrome | 2017-03-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000664658 | SCV001584345 | pathogenic | Alstrom syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn1639Lysfs*4) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs779366889, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome and/or cone-rod dystrophy (PMID: 25846608, 26992781). ClinVar contains an entry for this variant (Variation ID: 550038). For these reasons, this variant has been classified as Pathogenic. |
3billion | RCV000664658 | SCV002572884 | pathogenic | Alstrom syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant was found to in trans with other pathogenic variant (3billion dataset). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000550038 / PMID: 25846608). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |