ClinVar Miner

Submissions for variant NM_001846.4(COL4A2):c.4256T>C (p.Met1419Thr)

gnomAD frequency: 0.00059  dbSNP: rs191708663
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000317764 SCV000382688 benign Porencephaly 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000953671 SCV001100252 benign not provided 2024-11-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004549693 SCV004776468 likely benign COL4A2-related disorder 2019-03-07 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).
Ophthalmology Lab, The First People's Hospital of Yunnan Provience RCV004730931 SCV005326281 likely pathogenic concomitant exotropia 2024-08-30 no assertion criteria provided clinical testing Dominant inheritance. COL4A2 is a protein-coding gene associated with brain small vessel disease and intracerebral hemorrhage. Among its related pathways are the integrin pathway and nervous system development. Interestingly, ophthalmic diseases associated with COL4A2 mutations include keratoconus, ocular anterior segment dysgenesis, and nonarteritic anterior ischemic optic neuropathy. Neri et al described a novel COL4A2 mutation presenting with epilepsy and cortical development malformations, and the phenotype included strabismus. In our study, this gene was screened in all three pedigrees with different mutation sites.

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