Submissions for variant NM_001082486.2(ACD):c.413+1G>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002598709	SCV003488615	uncertain significance	Dyskeratosis congenita, autosomal dominant 6	2022-09-15	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs767285943, gnomAD 0.002%). This sequence change affects a donor splice site in intron 4 of the ACD gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ACD cause disease. This variant has not been reported in the literature in individuals affected with ACD-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
The Telomere Center at Johns Hopkins, Johns Hopkins University School of Medicine	RCV004565696	SCV005049648	pathogenic	Long telomere syndrome	2023-04-01	no assertion criteria provided	research