ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.2906C>G (rs35138315)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522361 SCV000617815 pathogenic not provided 2021-08-03 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31980526, 32723786, 12325029, 30647093, 25525159, 30406062, 29431110, 26346198, 24052634)
Fulgent Genetics,Fulgent Genetics RCV000763076 SCV000893587 pathogenic Alport syndrome, autosomal recessive 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000522361 SCV001228460 pathogenic not provided 2020-09-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser969*) in the COL4A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs35138315, ExAC 0.01%). This variant has been observed in individuals affected with Alport syndrome (PMID: 12325029, 24052634). ClinVar contains an entry for this variant (Variation ID: 449549). Loss-of-function variants in COL4A4 are known to be pathogenic (PMID: 11961012, 14582039, 19129241, 21196518, 24052634, 24522496, 24854265, 25307543, 26809805, 27281700). For these reasons, this variant has been classified as Pathogenic.
Cavalleri Lab, Royal College of Surgeons in Ireland RCV000763076 SCV001305529 pathogenic Alport syndrome, autosomal recessive 2020-05-27 criteria provided, single submitter research
Cavalleri Lab, Royal College of Surgeons in Ireland RCV001171331 SCV001328278 pathogenic Chronic kidney disease 2020-05-28 criteria provided, single submitter research PVS1, PS1
Baylor Genetics RCV000763076 SCV001525716 pathogenic Alport syndrome, autosomal recessive 2018-12-18 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Counsyl RCV000763076 SCV001132367 pathogenic Alport syndrome, autosomal recessive 2016-11-18 no assertion criteria provided clinical testing
Sydney Genome Diagnostics,Children's Hospital Westmead RCV001277168 SCV001449261 pathogenic Alport syndrome 2018-04-03 no assertion criteria provided clinical testing This individual is heterozygous for a pathogenic variant c.2906C>G in the COL4A4 gene. This variant creates a premature stop codon p.(Ser969*) and may result in a null allele due to nonsense-mediated mRNA decay. This variant has been widely reported in patients with autosomal recessive Alport syndrome (Storey et al 2013 J Am Soc Nephrol 24: 1945-1954), and some patients with thin basement membrane nephropathy (Buzza et al 2003 Kidney Int 63:447-453). This variant has been reported in the gnomAD browser (http://gnomad.broadinstitute.org) with a low allele frequency of 0.006% (18/ 277, 194 alleles). This variant is considered to be pathogenic according to the ACMG guidelines.
Natera, Inc. RCV001277168 SCV001464031 pathogenic Alport syndrome 2020-09-16 no assertion criteria provided clinical testing
Genomics England Pilot Project,Genomics England RCV001542734 SCV001760075 likely pathogenic Benign familial hematuria no assertion criteria provided clinical testing

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