ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7514G>A (p.Arg2505Gln) (rs147549623)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200965 SCV000149030 likely benign not specified 2018-02-19 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.
Invitae RCV000987583 SCV000153984 benign Familial adenomatous polyposis 1 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115121 SCV000183935 likely benign Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);Does not segregate with disease in family study (genes with incomplete penetrance);Other data supporting benign classification
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000200965 SCV000600150 likely benign not specified 2017-05-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115121 SCV000681872 likely benign Hereditary cancer-predisposing syndrome 2016-05-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589307 SCV000694119 benign not provided 2016-03-14 criteria provided, single submitter clinical testing Variant summary: The APC c.7514G>A variant affects a conserved nucleotide, resulting in amino acid change from Arg to Gln. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant was found in 102/125206 control chromosomes (1 homozygote) at a frequency of 0.0008147, which is about 14 times the maximal expected frequency of a pathogenic APC allele (0.0000602), suggesting this variant is benign. Thie variant has been reported in patients with MAP/FAP, CRC or pancreatic cancer. In one CRC family, this variant did not co-segregate with the disease (Zhou_2004), highly suggesting this variant is not causative. In addition, multiple clinical laboratories classified this variant as benign/likely benign. Taken together, this variant was classified as benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000589307 SCV000780824 likely benign not provided 2017-11-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000589307 SCV000805466 likely benign not provided 2017-02-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589307 SCV000888764 benign not provided 2018-05-31 criteria provided, single submitter clinical testing
Mendelics RCV000987583 SCV001136944 likely benign Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283366 SCV001156629 likely benign none provided 2019-11-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000589307 SCV000591211 likely benign not provided no assertion criteria provided clinical testing The p.Arg2505Gln variant was identified in 4 of 2376 proband chromosomes (frequency: 0.002) from individuals with colorectal adenomas or colorectal cancer (Azzopardi 2008, Lefevre 2012, Zhou 2004) and was present in 2 of 3862 control chromosomes (frequency: 0.001). The variant was also listed at a frequency of 0.001 in the “NHLBI Exome Sequencing Project”, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. In a study by Zhou (2004), the variant was found incidentally in two members of a family with hereditary colorectal cancer but did not segregate with disease in other affected family members. The variant was listed in dbSNP (ID: rs147549623) and the “InSiGHT Colon Cancer Database”, but was not identified in other databases searched, including HGMD, UMD and COSMIC. The p.Arg2505 residue is conserved in mammals and lower organisms; however, computational analyses (PolyPhen-2, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact of the variant amino acid to the protein and this information is not very predictive of pathogenicity. Additional study is needed to determine the clinical significance of this variant. 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 predicted benign.
True Health Diagnostics RCV000115121 SCV000693491 likely benign Hereditary cancer-predisposing syndrome 2017-07-31 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000589307 SCV001743394 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000589307 SCV001799220 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000589307 SCV001807141 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000589307 SCV001919711 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000589307 SCV001958207 likely benign not provided no assertion criteria provided clinical testing

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