Submissions for variant NM_017950.4(CCDC40):c.1338C>T (p.Leu446=)

gnomAD frequency: 0.04617  dbSNP: rs61734950

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150253	SCV000197258	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Leu446Leu in exon 9 of CCDC40: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 13.8% (578/4178) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs61734950).
PreventionGenetics, part of Exact Sciences	RCV000150253	SCV000313059	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094505	SCV000407182	benign	Primary ciliary dyskinesia 15	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000272314	SCV000558491	benign	Primary ciliary dyskinesia	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001705959	SCV001901045	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000272314	SCV002692708	benign	Primary ciliary dyskinesia	2016-09-30	criteria provided, single submitter	clinical testing	This alteration is classified as 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.