Submissions for variant NM_005559.4(LAMA1):c.2808+5G>A

gnomAD frequency: 0.00089  dbSNP: rs201030108

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000889841	SCV001033548	likely benign	not provided	2024-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000889841	SCV001820252	uncertain significance	not provided	2020-04-20	criteria provided, single submitter	clinical testing	Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and splice predictors support a deleterious effect; Reported in a patient with acute disseminated encephalomyelitis, optic neuritis, and periodic fever syndrome who also had variants identified in multiple other genes (Ledesma et al., 2019); This variant is associated with the following publications: (PMID: 31836009)
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004783869	SCV005397361	uncertain significance	Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome	2023-10-02	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (G>A) at position 2808+5 of the coding sequence of the LAMA1 gene exon 20 donor splice region. This is a previously reported variant (ClinVar 717102) that has been observed in an individuals affected by intellectual disability (PMID: 25167861). This variant is present in 345 of 281368 alleles (0.1226%) in the gnomAD population dataset. Multiple bioinformatic tools predict that this to base change will disrupt the donor splice site, and the G base at this position is highly conserved across the vertebrate species examined. Studies examining the functiol consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BS1, PP3
Mayo Clinic Laboratories, Mayo Clinic	RCV000889841	SCV005408576	uncertain significance	not provided	2024-07-26	criteria provided, single submitter	clinical testing	BS1, PP3, PS1_supporting
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000889841	SCV001807282	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000889841	SCV001965462	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004550069	SCV004771971	likely benign	LAMA1-related disorder	2019-10-01	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).