Submissions for variant NM_000038.6(APC):c.6510del (p.Glu2172fs)

dbSNP: rs1554087474

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000508107	SCV000600127	uncertain significance	not specified	2016-11-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000520383	SCV000618395	pathogenic	not provided	2017-04-14	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in APC is denoted c.6510delA at the cDNA level and p.Glu2172ArgfsX10 (E2172RfsX10) at the protein level. The normal sequence, with the base that is deleted in brackets, is AACC[delA]GGGGA. The deletion causes a frameshift which changes a Glutamic Acid to an Arginine at codon 2172, and creates a premature stop codon at position 10 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is expected to result in protein truncation and the last 672 correct amino acids are replaced by 9 incorrect ones. Based on the currently available information, we consider this variant to be pathogenic.
Myriad Genetics, Inc.	RCV004564249	SCV004044407	pathogenic	Familial adenomatous polyposis 1	2023-05-15	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics	RCV004943932	SCV005462657	pathogenic	Hereditary cancer-predisposing syndrome	2024-07-02	criteria provided, single submitter	clinical testing	The c.6510delA variant, located in coding exon 15 of the APC gene, results from a deletion of one nucleotide at nucleotide position 6510, causing a translational frameshift with a predicted alternate stop codon (p.E2172Rfs*10). This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 23% of the protein. However, premature stop codons are typically deleterious in nature, the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). This variant has been observed in at least one individual with a personal and/or family history that is consistent with APC-associated polyposis conditions (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this variant is interpreted as a disease-causing mutation.