ClinVar Miner

Submissions for variant NM_000038.6(APC):c.388A>G (p.Ser130Gly) (rs150973053)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122775 SCV000166032 benign Familial adenomatous polyposis 1 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129715 SCV000184518 likely benign Hereditary cancer-predisposing syndrome 2018-07-16 criteria provided, single submitter clinical testing Other data supporting benign classification;Subpopulation frequency in support of benign classification
GeneDx RCV000211891 SCV000209564 likely benign not specified 2017-10-23 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000211891 SCV000694040 benign not specified 2021-06-28 criteria provided, single submitter clinical testing Variant summary: APC c.388A>G (p.Ser130Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 253354 control chromosomes. The observed variant frequency is approximately 5 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is benign. c.388A>G has been reported in the literature in individuals. These reports do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. Co-occurrence with a pathogenic variant has been reported (APC c.3815C>G, p.Ser1272X), providing supporting evidence for a benign role. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign/likely benign n=7, VUS n=2). Based on the evidence outlined above, the variant was classified as benign.
Mendelics RCV000122775 SCV000838062 likely benign Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129715 SCV000902599 likely benign Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034387 SCV001133330 benign not provided 2019-02-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001155264 SCV001316683 uncertain significance APC-Associated Polyposis Disorders 2018-01-26 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034387 SCV001371504 likely benign not provided 2020-09-01 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034387 SCV000043104 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER _CC_NCGL, University of Washington RCV000417265 SCV000503532 uncertain significance Familial multiple polyposis syndrome 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 40 year old with a history of colon cancer diagnosed at age 39 and a family history of colon polyps.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000034387 SCV001552159 likely benign not provided no assertion criteria provided clinical testing The APC p.Ser130Gly variant was identified in 5 of 3188 proband chromosomes (frequency: 0.002) from individuals or families with FAP or atherosclerosis and was present in 1 of 1908 control chromosomes (frequency: 0.0005) from healthy individuals (Cleary 2008, De Rosa 2004, Johnston 2012). The variant was also identified in dbSNP (ID: rs150973053) as "With other allele ", ClinVar (classified as benign by Invitae; as likely benign by Ambry Genetics, GeneDx and one clinical laboratory; as uncertain significance by two clinical laboratories), MutDB, and in LOVD 3.0 (2x). The variant was not identified in COGR, Cosmic, UMD-LSDB or Zhejiang University databases. The variant was identified in control databases in 85 of 277202 chromosomes at a frequency of 0.0003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 4 of 6468 chromosomes (freq: 0.0006), Latino in 1 of 34420 chromosomes (freq: 0.00003), European in 4 of 126696 chromosomes (freq: 0.00003), Ashkenazi Jewish in 75 of 10150 chromosomes (freq: 0.007), Finnish in 1 of 25792 chromosomes (freq: 0.00004); it was not observed in the African, East Asian, or South Asian populations. The variant was identified with a co-occurring pathogenic APC variant (c.3815C>G, p.Ser1272*), increasing the likelihood that the p.Ser130Gly variant does not have clinical significance (De Rosa 2004). The p.Ser130 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.