ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1392+6A>G

dbSNP: rs4660848
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001069142 SCV001234290 uncertain significance Familial adenomatous polyposis 2 2024-01-11 criteria provided, single submitter clinical testing This sequence change falls in intron 14 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs4660848, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 862423). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001806013 SCV002052667 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-27 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +6 position of intron 14 of the MUTYH gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001806013 SCV002700691 uncertain significance Hereditary cancer-predisposing syndrome 2014-10-13 criteria provided, single submitter clinical testing The c.1476+6A>G intronic variant results from an A to G substitution 6 nucleotides after coding exon 14 in the MUTYH gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13,006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 28,000 alleles tested) in our clinical cohort. This nucleotide position is highly conserved in available higher vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this donor splice site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of c.1476+6A>G remains unclear.

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