Submissions for variant NM_001330360.2(POLA1):c.2566+6G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003680259	SCV004409954	uncertain significance	not provided	2022-12-02	criteria provided, single submitter	clinical testing	This sequence change falls in intron 23 of the POLA1 gene. It does not directly change the encoded amino acid sequence of the POLA1 protein. It affects a nucleotide within the consensus splice site. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with POLA1-related conditions. This variant is not present in population databases (gnomAD no frequency).
PreventionGenetics, part of Exact Sciences	RCV003901253	SCV004716435	likely benign	POLA1-related disorder	2020-12-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).