Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV004019697 | SCV000166015 | benign | Familial adenomatous polyposis 1 | 2025-01-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000164173 | SCV000214791 | likely benign | Hereditary cancer-predisposing syndrome | 2014-07-24 | 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. |
Illumina Laboratory Services, |
RCV000318991 | SCV000451989 | likely benign | APC-Associated Polyposis Disorders | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Color Diagnostics, |
RCV000164173 | SCV000681468 | benign | Hereditary cancer-predisposing syndrome | 2016-03-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587584 | SCV000693998 | benign | not provided | 2017-06-09 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.1488A>T (p.Thr496Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 55/121488 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.006028 (52/8626). This frequency is about 84 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000587584 | SCV000887507 | benign | not provided | 2023-03-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000587584 | SCV001830129 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000164173 | SCV002536394 | benign | Hereditary cancer-predisposing syndrome | 2021-03-19 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000508123 | SCV002550585 | likely benign | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV004019697 | SCV004931835 | benign | Familial adenomatous polyposis 1 | 2024-03-04 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Department of Pathology and Laboratory Medicine, |
RCV001356780 | SCV001552041 | benign | Carcinoma of colon | no assertion criteria provided | clinical testing | The APC p.Thr496= variant was identified in 1 of 338 proband chromosomes (frequency: 0.01) from individuals or families with colorectal cancer, and was not identified in 244 control chromosomes from healthy individuals (Chang 2016, Chen 2006). The variant was also identified in dbSNP (ID: rs9282599) as “With Likely benign allele”, ClinVar (classified as benign by Invitae, Color Genomics and Integrated Genetics/Laboratory Corporation of America; as likely benign by Ambry Genetics and Quest Diagnostics Nichols Institute San Juan Capistrano), Clinvitae, LOVD 3.0 (Probably does not affect function), or Zhejiang Colon Cancer Database (2X). The variant was not identified in GeneInsight-COGR, Cosmic, or UMD-LSDB databases. The variant was identified in control databases in 123 of 277014 chromosomes (1 homozygous) at a frequency of 0.0004 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include East Asian in 122 of 18852 chromosomes (freq: 0.01), Finnish in 1 of 25786 chromosomes (freq: 0.00004), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, and South Asian populations. The p.Thr496= 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, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. | |
Clinical Genetics, |
RCV000508123 | SCV001920993 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000587584 | SCV001954828 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000587584 | SCV001965219 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
RCV003952620 | SCV004775238 | benign | APC-related disorder | 2019-07-11 | no assertion criteria provided | clinical testing | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |