Submissions for variant NM_001048174.2(MUTYH):c.-6-7G>A

gnomAD frequency: 0.00010  dbSNP: rs780029247

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000198929	SCV000253354	likely benign	Familial adenomatous polyposis 2	2024-01-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579890	SCV000685617	likely benign	Hereditary cancer-predisposing syndrome	2016-07-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000855652	SCV000697692	likely benign	not specified	2023-09-11	criteria provided, single submitter	clinical testing	Variant summary: MUTYH c.37-7G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00013 in 251438 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MUTYH causing MUTYH-Associated Polyposis (0.00013 vs 0.0046), allowing no conclusion about variant significance. c.37-7G>A has been reported in the literature as a VUS in settings of multigene panel testing on individuals affected with breast/colorectal cancer (example, Tung_2015, Yurgelun_2015). These report(s) do not provide unequivocal conclusions about association of the variant with MUTYH-Associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Counsyl	RCV000198929	SCV000800018	likely benign	Familial adenomatous polyposis 2	2018-05-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000589838	SCV000806357	likely benign	not provided	2017-06-02	criteria provided, single submitter	clinical testing
Mendelics	RCV000198929	SCV001135270	likely benign	Familial adenomatous polyposis 2	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000589838	SCV001944779	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000579890	SCV002532279	likely benign	Hereditary cancer-predisposing syndrome	2021-05-29	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589838	SCV002774205	likely benign	not provided	2022-09-05	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000198929	SCV004016032	likely benign	Familial adenomatous polyposis 2	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000855652	SCV004243216	likely benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000198929	SCV004823357	likely benign	Familial adenomatous polyposis 2	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589838	SCV005262076	likely benign	not provided		criteria provided, single submitter	not provided