Submissions for variant NM_012472.6(DNAAF11):c.1391C>T (p.Pro464Leu)

gnomAD frequency: 0.00036  dbSNP: rs139131485

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243911	SCV000311951	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000767176	SCV000536293	uncertain significance	not provided	2017-01-31	criteria provided, single submitter	clinical testing	The P464L variant in the LRRC6 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, P464L was observed with an allele frequency of 0.72% in individuals of South Asian ancestry the Exome Aggregation Consortium (ExAC) data set, indicating it may be a rare variant in this population. The P464L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P464L as a variant of uncertain significance.
Invitae	RCV001085911	SCV001091727	likely benign	Primary ciliary dyskinesia 19	2024-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001085911	SCV001322967	uncertain significance	Primary ciliary dyskinesia 19	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, 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.
Ambry Genetics	RCV002461049	SCV002756030	benign	Primary ciliary dyskinesia	2017-10-30	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.
Department of Molecular Bıology and Genetics, Istanbul Technical University	RCV001823000	SCV002072581	risk factor	Multiple sclerosis, susceptibility to		no assertion criteria provided	research	A family with 4 affected and 4 unaffected members was analyzed. The variant is segregated with MS in a fully penetrant manner in the family.