ClinVar Miner

Submissions for variant NM_201525.4(ADGRG1):c.739_745del (p.Gln247fs) (rs587776625)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000006184 SCV000247497 pathogenic Polymicrogyria, bilateral frontoparietal 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000351326 SCV000329765 pathogenic not provided 2018-11-19 criteria provided, single submitter clinical testing The c.739_745delCAGGACC pathogenic variant in the ADGRG1 gene has been reported previously as a homozygous variant in multiple individuals with bilateral frontoparietal polymicrogyria (BFPP) (Piao et al., 2004). Due to use of alternative nomenclature, this variant was reported as c.739_746delCAGGACC (Piao et al., 2004). The deletion causes a frameshift starting with codon Glutamine 247, changes this amino acid to a Cysteine residue and creates a premature Stop codon at position 74 of the new reading frame, denoted p.Gln247CysfsX74. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000351326 SCV000937548 pathogenic not provided 2019-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln247Cysfs*74) in the ADGRG1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs749257776, ExAC 0.04%). This variant has been observed in several individuals affected with bilateral frontoparietal polymicrogyria (PMID: 15044805). This variant is also known as 739_746delCAGGACC in the literature. ClinVar contains an entry for this variant (Variation ID: 5828). Loss-of-function variants in ADGRG1 are known to be pathogenic (PMID: 15044805, 20929962). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006184 SCV000026366 pathogenic Polymicrogyria, bilateral frontoparietal 2004-03-26 no assertion criteria provided literature only
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000006184 SCV000778444 pathogenic Polymicrogyria, bilateral frontoparietal 2018-08-24 no assertion criteria provided clinical testing The observed variant c.739_745delCAGGACC (p.Gln247CysfsTer74) is not reported in 1000 Genomes and its minor allele frequency in the ExAC database is 0.006%. The in silico prediction of the given variant is disease causing by MutationTaster2.

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