Submissions for variant NM_213599.3(ANO5):c.1898+1G>A

gnomAD frequency: 0.00009  dbSNP: rs142027093

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000479758	SCV000226710	pathogenic	not provided	2017-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000479758	SCV000567319	pathogenic	not provided	2021-11-24	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate this nucleotide change results in the out-of-frame exclusion of exons 15, 16, and 17 (Wahbi et al., 2013); This variant is associated with the following publications: (PMID: 23041008, 23663589, 23530687, 30919934, 23670307, 31127727, 23606453, 23607914, 32925086, 32528171, 33458579, 32819793, 31980526)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000627783	SCV000645879	pathogenic	Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 17 of the ANO5 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 ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276, 30919934). This variant is present in population databases (rs142027093, gnomAD 0.02%). Disruption of this splice site has been observed in individuals with autosomal recessive ANO5-related conditions (PMID: 23041008, 23530687, 23606453, 23607914, 23663589, 23670307). ClinVar contains an entry for this variant (Variation ID: 194805). 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.
Fulgent Genetics, Fulgent Genetics	RCV000762832	SCV000893191	pathogenic	Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L; Miyoshi muscular dystrophy 3	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000479758	SCV001143032	pathogenic	not provided	2019-06-17	criteria provided, single submitter	clinical testing	The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000479758	SCV001247611	pathogenic	not provided	2022-03-01	criteria provided, single submitter	clinical testing	ANO5: PM3:Very Strong, PVS1, PM2, PP4, PS3:Supporting
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV001270118	SCV001448980	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2L	2019-09-06	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000479758	SCV001714374	pathogenic	not provided	2021-02-24	criteria provided, single submitter	clinical testing	PVS1, PS3, PS4_moderate, PM3_very strong, PM2
Revvity Omics, Revvity	RCV000479758	SCV002017114	pathogenic	not provided	2023-09-25	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000479758	SCV001742014	pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000479758	SCV001798183	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000479758	SCV001920569	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000479758	SCV001974466	pathogenic	not provided		no assertion criteria provided	clinical testing