Submissions for variant NM_000038.6(APC):c.5250C>T (p.Val1750=)

dbSNP: rs2229997

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163958	SCV000214556	likely benign	Hereditary cancer-predisposing syndrome	2014-12-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV003534435	SCV000252928	benign	Familial adenomatous polyposis 1	2024-01-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000200153	SCV000488420	likely benign	Familial adenomatous polyposis 1	2016-03-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163958	SCV000681719	likely benign	Hereditary cancer-predisposing syndrome	2016-10-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000859105	SCV001133346	benign	not provided	2019-01-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001174930	SCV001338373	likely benign	not specified	2020-02-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000859105	SCV001875418	benign	not provided	2015-05-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163958	SCV002535098	likely benign	Hereditary cancer-predisposing syndrome	2021-05-26	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000200153	SCV004017803	benign	Familial adenomatous polyposis 1	2023-02-16	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.
PreventionGenetics, part of Exact Sciences	RCV003954966	SCV004782603	likely benign	APC-related condition	2023-02-16	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000859105	SCV001549884	likely benign	not provided		no assertion criteria provided	clinical testing	The APC p.Val1750= variant was not identified in the literature nor was it identified in the following databases: MutDB, UMD-LSDB, Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs2229997) as “With Likely benign allele”, ClinVar (as likely benign by Ambry Genetics, Invitae, Counsyl, and Color Genomics), Clinvitae (2x), Cosmic (in a tumour in the large intestine), and LOVD 3.0 (1x). The variant was identified in control databases in 13 of 245396 chromosomes at a frequency of 0.000053 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: European (Non-Finnish) in 1 of 111010 chromosomes (freq: 0.000009), and Ashkenazi Jewish in 12 of 9812 chromosomes (freq: 0.001223); it was not observed in the African, Other, Latino, East Asian, European (Finnish), and South Asian populations. The p.Val1750= 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 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.