Submissions for variant NM_001242957.3(MAK):c.156+2T>C

dbSNP: rs1201940872

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000592868	SCV000702816	likely pathogenic	not provided	2016-11-22	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001075494	SCV001241118	likely pathogenic	Retinal dystrophy	2018-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000592868	SCV002304608	likely pathogenic	not provided	2023-02-18	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects a donor splice site in intron 2 of the MAK 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), and loss-of-function variants in MAK are known to be pathogenic (PMID: 21148103, 21825139, 24938718, 29781741). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MAK-related conditions. ClinVar contains an entry for this variant (Variation ID: 498012). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.