Submissions for variant NM_001048174.2(MUTYH):c.264+11G>A

gnomAD frequency: 0.00044  dbSNP: rs139977567

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000126891	SCV000170422	benign	not specified	2014-04-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000380650	SCV000357906	likely benign	Familial adenomatous polyposis 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000580271	SCV000685612	benign	Hereditary cancer-predisposing syndrome	2016-05-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000126891	SCV000806354	benign	not specified	2017-08-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000380650	SCV002337108	benign	Familial adenomatous polyposis 2	2024-02-01	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000126891	SCV002552523	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354112	SCV001548645	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The MUTYH c.348+11G>A variant was identified in 1 of 110 proband chromosomes (frequency: 0.001) from individuals or families with lung cancer (Shinmura 2001). The variant was also identified in dbSNP (ID: rs139977567) as With Uncertain significance allele, ClinVar (classified as benign by GeneDx; classified as uncertain significance by Illumina), Clinvitae, Insight Colon Cancer Gene Variant Database, databases. The variant was not identified in UMD-LSDB database. The variant was identified in control databases in 445 (8 homozygous) of 277170 chromosomes at a frequency of 0.0016 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000126891	SCV001798937	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000126891	SCV001917815	benign	not specified		no assertion criteria provided	clinical testing