Submissions for variant NM_033380.3(COL4A5):c.2692A>G (p.Met898Val)

gnomAD frequency: 0.00017  dbSNP: rs104886192

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000885639	SCV001029101	benign	not provided	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000885639	SCV001863032	benign	not provided	2020-10-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30773290, 11223851, 25525159, 20378821)
Centogene AG - the Rare Disease Company	RCV000021433	SCV002028342	benign	X-linked Alport syndrome	2021-08-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000885639	SCV004167398	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	COL4A5: BS2
Laboratory of Prof. Karen Avraham, Tel Aviv University	RCV000021433	SCV005073737	pathogenic	X-linked Alport syndrome	2024-05-01	criteria provided, single submitter	research	Pathogenic by Deafness Variation Database based on PMID:30773290
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767014	SCV005381640	likely benign	not specified	2024-08-01	criteria provided, single submitter	clinical testing	Variant summary: COL4A5 c.2692A>G (p.Met898Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 1203910 control chromosomes, including 85 hemizygotes (gnomAD v4.1.0). c.2692A>G has been reported in the literature in individuals with clinical features of Alport syndrome (e.g., Barker_2001, Connaughton_2019, Uliana_2021), however these report(s) do not provide unequivocal conclusions about association of the variant with Alport Syndrome 1, X-Linked Recessive. Co-occurrences with other pathogenic variant(s) have been reported (INF2 c.353T>A, p.Ile118Asn), providing supporting evidence for a benign role (Connaughton_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 11223851, 30773290, 33369211). ClinVar contains an entry for this variant (Variation ID: 24554). Based on the evidence outlined above, the variant was classified as likely benign.
Medical Genetics, University of Parma	RCV000021433	SCV001245123	pathogenic	X-linked Alport syndrome	2020-03-11	flagged submission	clinical testing
Genome-Nilou Lab	RCV000021433	SCV001737201	uncertain significance	X-linked Alport syndrome	2021-05-18	flagged submission	clinical testing
Natera, Inc.	RCV000021433	SCV002083650	likely benign	X-linked Alport syndrome	2020-01-15	no assertion criteria provided	clinical testing
Yale Center for Mendelian Genomics, Yale University	RCV001849276	SCV002106605	pathogenic	Autosomal dominant Alport syndrome	2019-02-14	flagged submission	literature only
PreventionGenetics, part of Exact Sciences	RCV003904858	SCV004720696	likely benign	COL4A5-related disorder	2019-06-15	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).