Submissions for variant NM_001369268.1(ACAN):c.6912C>A (p.Cys2304Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002676998	SCV002993957	pathogenic	not provided	2023-09-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1952466). This variant has not been reported in the literature in individuals affected with ACAN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys2304*) in the ACAN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACAN are known to be pathogenic (PMID: 16080123, 24762113).
PreventionGenetics, part of Exact Sciences	RCV004548352	SCV004107075	likely pathogenic	ACAN-related disorder	2022-11-17	criteria provided, single submitter	clinical testing	The ACAN c.6912C>A variant is predicted to result in premature protein termination (p.Cys2304*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in ACAN are expected to be pathogenic for autosomal dominant idiopathic short stature with or without additional features (Hauer et al. 2017. PubMed ID: 28939912). This variant is interpreted as likely pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV002676998	SCV004704330	pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ACAN: PVS1, PM2