Submissions for variant NM_145038.5(DRC1):c.352C>T (p.Gln118Ter)

gnomAD frequency: 0.00031  dbSNP: rs142371860

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725468	SCV000337157	likely pathogenic	not provided	2015-11-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000549203	SCV000624510	pathogenic	Primary ciliary dyskinesia	2024-12-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln118*) in the DRC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DRC1 are known to be pathogenic (PMID: 23354437, 31960620). This variant is present in population databases (rs142371860, gnomAD 0.07%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with primary ciliary dyskinesia (PMID: 23354437). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 55840). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000049261	SCV000893604	pathogenic	Primary ciliary dyskinesia 21	2018-10-31	criteria provided, single submitter	clinical testing
Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS)	RCV002254519	SCV002525500	pathogenic	Primary ciliary dyskinesia; Primary ciliary dyskinesia 21		criteria provided, single submitter	clinical testing	We analyzed the expression of DRC1 of a patient with this mutation and observed that mRNA was downregulated as well as its protein were also decreased.
GeneDx	RCV000725468	SCV002549228	pathogenic	not provided	2022-06-02	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27996046, 23354437, 30487145, 12746204, 26582918, 34426522, 27535533)
OMIM	RCV000049261	SCV000077514	pathogenic	Primary ciliary dyskinesia 21	2013-03-01	no assertion criteria provided	literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825030	SCV000966227	uncertain significance	not specified	2018-03-16	flagged submission	clinical testing	Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gln118X ( NM145038.2 c.352C>T) variant in DRC1 has been previously reported in 2 homozygou s individuals with primary ciliary dyskinesia and segregated in 1 affected homoz ygous family member in 1 family (Wirschell 2013). Mutant studies and studies fro m patient cells with the p.Gln118X variant report an impact to protein function (Wirschell 2013). This variant has also been reported in ClinVar as likely patho genic (Variation ID#55840). It has been identified in 0.066% (83/126650) of Euro pean chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitut e.org; rs142371860). Although this variant has been seen in the general populati on, its frequency is low enough to be consistent with a recessive carrier freque ncy. This nonsense variant leads to a premature termination codon at position 11 8, which is predicted to lead to a truncated or absent protein. In summary, ther e is suspicion for a pathogenic role; however, the gene-disease association bet ween DRC1 is currently assessed at a moderate level.
PreventionGenetics, part of Exact Sciences	RCV004752736	SCV005364720	likely pathogenic	DRC1-related disorder	2024-07-01	no assertion criteria provided	clinical testing	The DRC1 c.352C>T variant is predicted to result in premature protein termination (p.Gln118*). This variant has been reported in the homozygous state in three affected individuals from two families with primary ciliary dyskinesia, and segregated with the disease in these families (Supplementary Figure 3, Wirschell et al. 2013. PubMed ID: 23354437). This variant is reported in 0.067% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including 1 homozygote. Nonsense variants in DRC1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.