ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7150T>A (p.Leu2384Ile)

gnomAD frequency: 0.00003  dbSNP: rs755345693
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491662 SCV000579877 benign Hereditary cancer-predisposing syndrome 2021-10-20 criteria provided, single submitter clinical testing This alteration is classified as 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000698172 SCV000826817 likely benign Familial adenomatous polyposis 1 2024-01-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000491662 SCV000909625 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-02 criteria provided, single submitter clinical testing This missense variant replaces leucine with isoleucine at codon 2384 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 7/250266 chromosomes in the general population by the Genome Aggregation Database (gnomAD) and in multiple healthy control individuals (PMID: 32980694). 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000698172 SCV001737429 uncertain significance Familial adenomatous polyposis 1 2021-06-10 criteria provided, single submitter clinical testing The APC c.7150T>A (p.Leu2384Ile) missense change has a maximum subpopulation frequency of 0.038% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/5-112178441-T-A?dataset=gnomad_r2_1). Five of six in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with familial adenomatous polyposis. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.
Sema4, Sema4 RCV000491662 SCV002527468 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-13 criteria provided, single submitter curation
GeneDx RCV002282173 SCV002571441 uncertain significance not provided 2022-03-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV004003445 SCV004843508 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces leucine with isoleucine at codon 2384 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 7/250266 chromosomes in the general population by the Genome Aggregation Database (gnomAD) and in multiple healthy control individuals (PMID: 32980694). 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.
Baylor Genetics RCV000698172 SCV005053796 uncertain significance Familial adenomatous polyposis 1 2024-02-19 criteria provided, single submitter clinical testing

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