Submissions for variant NM_017777.4(MKS1):c.1024+1G>A

gnomAD frequency: 0.00002  dbSNP: rs199874059

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668139	SCV000792690	likely pathogenic	Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28	2017-07-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001038005	SCV001201446	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 11 of the MKS1 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 MKS1 are known to be pathogenic (PMID: 19466712, 24886560, 26490104). This variant is present in population databases (rs199874059, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with Meckel-Gruber syndrome (PMID: 17377820). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS11+1G>A. ClinVar contains an entry for this variant (Variation ID: 1391). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001570919	SCV001795291	likely pathogenic	not provided	2021-04-08	criteria provided, single submitter	clinical testing	Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17377820, 25525159)
Revvity Omics, Revvity	RCV001570919	SCV002023477	likely pathogenic	not provided	2022-06-17	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003472957	SCV004194918	pathogenic	Bardet-Biedl syndrome 13	2024-03-06	criteria provided, single submitter	clinical testing
OMIM	RCV000022414	SCV000043099	pathogenic	Meckel syndrome, type 1	2007-06-01	no assertion criteria provided	literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000022414	SCV000082434	probable-pathogenic	Meckel syndrome, type 1		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.