Submissions for variant NM_181426.2(CCDC39):c.1871_1872del (p.Ile624fs)

dbSNP: rs1560086701

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000684853	SCV000812313	pathogenic	Primary ciliary dyskinesia	2024-04-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile624Lysfs*3) in the CCDC39 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCDC39 are known to be pathogenic (PMID: 21131972, 23255504). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 565319). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000684853	SCV002723202	pathogenic	Primary ciliary dyskinesia	2017-11-20	criteria provided, single submitter	clinical testing	The c.1871_1872delTA pathogenic mutation, located in coding exon 13 of the CCDC39 gene, results from a deletion of two nucleotides at nucleotide positions 1871 to 1872, causing a translational frameshift with a predicted alternate stop codon (p.I624Kfs*3). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
PreventionGenetics, part of Exact Sciences	RCV003420209	SCV004116367	pathogenic	CCDC39-related disorder	2023-02-28	criteria provided, single submitter	clinical testing	The CCDC39 c.1871_1872delTA variant is predicted to result in a frameshift and premature protein termination (p.Ile624Lysfs*3). This variant has been reported in the homozygous state in multiple individuals with Primary ciliary dyskinesia (Monies et al. 2019. PubMed ID: 31130284. Table S1; Fassad et al. 2019. PubMed ID: 31879361). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in CCDC39 are expected to be pathogenic. This variant is interpreted as pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV004760699	SCV005374030	pathogenic	Primary ciliary dyskinesia 14	2024-09-22	criteria provided, single submitter	clinical testing
Pediatric Genetics Clinic, Sheba Medical Center	RCV001731885	SCV001572808	likely pathogenic	Heterotaxy	2021-04-24	no assertion criteria provided	research