ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5481G>A (p.Ser1827=)

gnomAD frequency: 0.00002  dbSNP: rs775867327
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001720157 SCV000522754 likely benign not provided 2020-11-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001720157 SCV000556285 likely benign not provided 2023-12-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567088 SCV000671496 likely benign Hereditary cancer-predisposing syndrome 2016-01-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354167 SCV001548711 likely benign Carcinoma of colon no assertion criteria provided clinical testing The POLE p.Ser1827= variant was not identified in the literature nor was it identified in the Cosmic database. The variant was identified in dbSNP (ID: rs775867327) as "With Likely benign allele ", and in ClinVar (classified as likely benign by GeneDx, Invitae, Ambry Genetics). The variant was identified in control databases in 2 of 246210 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 15302 chromosomes (freq: 0.000065), European in 1 of 111684 chromosomes (freq: 0.000009), but was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Ser1827= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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.

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