Submissions for variant NM_033380.3(COL4A5):c.2858G>T (p.Gly953Val)

gnomAD frequency: 0.00119  dbSNP: rs78972735

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000021452	SCV000267267	uncertain significance	X-linked Alport syndrome	2016-03-18	criteria provided, single submitter	reference population
Eurofins Ntd Llc (ga)	RCV000598479	SCV000700762	benign	not specified	2016-12-13	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000598479	SCV000732049	benign	not specified	2017-12-21	criteria provided, single submitter	clinical testing	p.Gly953Val in exon 33 of COL4A5: This variant is not expected to have clinica l significance, because it has been identified in 3.7% (513/13865) of East Asian chromosomes including 7 homozygotes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs104886203, rs78972735). Although it has been reported in several individuals with Alport syndrome or hearing loss, 2 individuals with Alport syndrome had another COL4A5 variant in cis with this va riant, and one individual was reported to have polycystic kidney disease with no additional clinical features of Alport syndrome (Knebelmann 1996, Lennon 2015, Miao 2017, Miyagawa 2013, Nishio 2015, Randles 2016, Tan 2010). In summary, it s frequency is too high to be causative for Alport syndrome. ACMG/AMP criteria a pplied: BA1
Athena Diagnostics	RCV000598479	SCV000841178	benign	not specified	2019-10-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000710871	SCV001021332	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000021452	SCV001141995	benign	X-linked Alport syndrome	2023-08-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000021452	SCV001716348	benign	X-linked Alport syndrome	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000710871	SCV001949048	benign	not provided	2019-09-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22995991, 28827396, 30577881, 30367527, 25739341, 23967202, 8940267, 30245029, 31138263, 28476686, 31180159, 32038292)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002293989	SCV002587478	benign	Kidney disorder	2021-06-24	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000021452	SCV002083652	benign	X-linked Alport syndrome	2020-07-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952369	SCV004767025	benign	COL4A5-related disorder	2022-06-20	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).