Submissions for variant NM_001277115.2(DNAH11):c.5132A>G (p.Gln1711Arg)

gnomAD frequency: 0.00031  dbSNP: rs189432084

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000205408	SCV000259363	likely benign	Primary ciliary dyskinesia	2024-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000205408	SCV000468109	uncertain significance	Primary ciliary dyskinesia	2016-06-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000600436	SCV000711300	likely benign	not specified	2017-04-03	criteria provided, single submitter	clinical testing	p.Gln1711Arg in exon 30 of DNAH11: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, shrew, tenrec, and platypus have an arginine (Arg) at this position desp ite high nearby amino acid conservation. In addition, computational prediction t ools do not suggest a high likelihood of impact to the protein. It has also been identified in 0.2% (48/26256) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs189432084).
CeGaT Center for Human Genetics Tuebingen	RCV000998771	SCV001155045	uncertain significance	not provided	2016-05-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000205408	SCV002641043	benign	Primary ciliary dyskinesia	2015-01-12	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.
PreventionGenetics, part of Exact Sciences	RCV003955223	SCV004774203	uncertain significance	DNAH11-related condition	2023-12-04	criteria provided, single submitter	clinical testing	The DNAH11 c.5132A>G variant is predicted to result in the amino acid substitution p.Gln1711Arg. This variant has been reported along with additional DNAH11 variants in individuals with primary ciliary dyskinesia (Table 4, Sherman et al. 2020. PubMed ID: 32662935; Alsamri et al. 2021. PubMed ID: 34768622). This variant is reported in 0.081% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.