Submissions for variant NM_000092.5(COL4A4):c.2045A>G (p.Asp682Gly)

gnomAD frequency: 0.00001  dbSNP: rs142093416

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000490277	SCV000267266	uncertain significance	Autosomal recessive Alport syndrome	2016-03-18	criteria provided, single submitter	reference population
Counsyl	RCV000490277	SCV000793173	uncertain significance	Autosomal recessive Alport syndrome	2017-07-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001140967	SCV001301276	uncertain significance	Alport syndrome	2017-07-13	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001582719	SCV001811303	uncertain significance	not provided	2021-05-19	criteria provided, single submitter	clinical testing	Observed in the heterozygous state in a individual with hearing loss in the published literature, however, information was limited (Miyagawa et al., 2013); Observed in a patient with thin basement nephropathy in the published literature; this variant was also noted in the same study to be observed in 143 controls in the Korean population (Baek et al., 2009); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease; This variant is associated with the following publications: (PMID: 19675380, 23967202)
3billion	RCV000490277	SCV002058564	uncertain significance	Autosomal recessive Alport syndrome	2022-01-03	criteria provided, single submitter	clinical testing	Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL4A4 related disorder (PMID:23967202, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000072, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Natera, Inc.	RCV001140967	SCV002078909	uncertain significance	Alport syndrome	2020-02-12	no assertion criteria provided	clinical testing