ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.2420del (p.Gly807fs)

dbSNP: rs786205640
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre RCV000171505 SCV000221704 likely pathogenic not provided criteria provided, single submitter research
GeneDx RCV000171505 SCV000568822 pathogenic not provided 2017-01-23 criteria provided, single submitter clinical testing The c.2420delG variant in the COL4A4 gene has been reported previously in association with autosomal recessive Alport syndrome when present in the homozygous state or when in trans with another disease-causing variant (Ramzan et al., 2014; Anazi et al., 2014). In addition, family members heterozygous for the c.2420delG variant were reported with considerable phenotypic variability, ranging from intermittent hematuria to late onset end stage renal disease (Ramzan et al., 2014). The c.2420delG variant causes a frameshift starting with codon Glycine 807, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 62 of the new reading frame, denoted p.Gly807ValfsX62. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2420delG variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2420delG as a pathogenic variant.
3billion RCV001808445 SCV002058910 pathogenic Autosomal recessive Alport syndrome 2022-01-03 criteria provided, single submitter clinical testing Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000191313, PMID:23551117). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV001808445 SCV004807138 uncertain significance Autosomal recessive Alport syndrome 2024-03-26 criteria provided, single submitter clinical testing

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