Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003771046 | SCV001585576 | pathogenic | Familial adenomatous polyposis 1 | 2014-09-09 | criteria provided, single submitter | clinical testing | For these reasons, this sequence change has been classified as Pathogenic. This sequence change has been reported in patients affected with FAP (PMID: 12010888, 16088911, 10634400) and it is not present in population databases. This sequence change results in the deletion of two nucleotides in exon 16 of the APC mRNA (c.2928_2929delAG). It results in a frameshift at codon 977 which leads to a premature translational stop signal 6 codons downstream (p.Gly977Serfs*7). It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002438825 | SCV002748761 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-11 | criteria provided, single submitter | clinical testing | The c.2928_2929delAG pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of two nucleotides at nucleotide positions 2928 to 2929, causing a translational frameshift with a predicted alternate stop codon (p.G977Sfs*7). This alteration has been reported in several patients affected with familial adenomatous polyposis (Cetta F et al. J. Clin. Endocrinol. Metab. 2000 Jan;85:286-92; Moisio AL et al. Gut. 2002 Jun;50:845-50; Kim DW et al. Hum. Mutat. 2005 Sep;26:281; Lagarde A et al. J. Med. Genet. 2010 Oct;47:721-2). Of note, this alteration is also designated as c.2927_2928delGA in the published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
| Department of Pathology and Laboratory Medicine, |
RCV001357563 | SCV001553069 | likely pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The APC p.Gly977Serfs*7 variant was identified in 3 of 1864 proband chromosomes (frequency: 0.002) from individuals or families with familial adenomatous polyposis (Kim 2005, Lagarde 2010, Moisio 2002). The variant was also identified in Cosmic (1x in Large intestine), LOVD 3.0 (3x), UMD-LSDB (3x as causal), and in Insight Hereditary Tumors (3x) databases. The variant was not identified in dbSNP, ClinVar, Clinvitae, COGR, or Zhejiang University databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.2928_2929del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 977 and leads to a premature stop codon at position 983. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in APC associated cancers and is the type of variant expected to cause the disorder. 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 pathogenic role for this variant. This variant is classified as likely pathogenic. |