Submissions for variant NM_017950.4(CCDC40):c.1123A>C (p.Lys375Gln)

gnomAD frequency: 0.00943  dbSNP: rs61734951

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000231612	SCV000290392	benign	Primary ciliary dyskinesia	2024-01-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000244324	SCV000313053	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094545	SCV000407178	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000244324	SCV000966265	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Lys375Gln in exon 7 of CCDC40: This variant is not expected to have clinical sig nificance because it has been identified in 1.5% (63/4160) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs61734951).
Ambry Genetics	RCV000231612	SCV002750620	benign	Primary ciliary dyskinesia	2018-04-20	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001094545	SCV004563995	likely benign	Primary ciliary dyskinesia 15	2023-08-30	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573064	SCV001798388	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573064	SCV001972517	likely benign	not provided		no assertion criteria provided	clinical testing