Submissions for variant NM_017950.4(CCDC40):c.850G>C (p.Asp284His)

gnomAD frequency: 0.00099  dbSNP: rs201042940

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000244307	SCV000313116	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094519	SCV000407173	uncertain significance	Primary ciliary dyskinesia 15	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000399959	SCV000558503	benign	Primary ciliary dyskinesia	2024-01-31	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000244307	SCV000711284	benign	not specified	2017-03-20	criteria provided, single submitter	clinical testing	p.Asp284His in exon 5 of CCDC40: This variant is not expected to have clinical s ignificance because it has been identified in 1% (129/1262) of South Asian chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs201042940).
GeneDx	RCV001544955	SCV001764187	likely benign	not provided	2020-03-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 33574797)
Ambry Genetics	RCV000399959	SCV002681540	benign	Primary ciliary dyskinesia	2016-09-15	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.
CeGaT Center for Human Genetics Tuebingen	RCV001544955	SCV004144424	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	CCDC40: BP4, BS2
MAGI's Lab - Research, MAGI Group	RCV001283738	SCV001432681	uncertain significance	Male infertility		no assertion criteria provided	provider interpretation