Submissions for variant NM_023036.6(DNAI2):c.1574C>T (p.Ala525Val)

gnomAD frequency: 0.00036  dbSNP: rs145602856

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232038	SCV000290684	likely benign	Primary ciliary dyskinesia	2024-12-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094498	SCV000406370	uncertain significance	Primary ciliary dyskinesia 9	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000613204	SCV000711308	likely benign	not specified	2016-06-07	criteria provided, single submitter	clinical testing	The p.Ala525Val in exon 12 of DNAI2: This variant is not expected to have clinic al significance because it has been identified in 0.9% (74/8618) of East Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs145602856) and due to a lack of conservation in mammals. Of note, six mammals have a valine (V) at this position despite high nearby amino acid co nservation.
Pars Genome Lab	RCV001094498	SCV001736795	likely benign	Primary ciliary dyskinesia 9	2021-05-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000232038	SCV002703584	uncertain significance	Primary ciliary dyskinesia	2015-04-08	criteria provided, single submitter	clinical testing	The p.A525V variant (also known as c.1574C>T), located in coding exon 11 of the DNAI2 gene, results from a C to T substitution at nucleotide position 1574. The alanine at codon 525 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs145602856. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.14% (3/2098) total alleles studied. The highest observed frequency was 0.59% (1/170) CEPH alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.02% (2/13006) total alleles studied, having been observed in 0.02% (1/4406) African American alleles and 0.01% (1/8600) European American alleles. This amino acid position is poorly conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence for this variant is limited at this time, the clinical significance of this variant remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV003417837	SCV004144144	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	DNAI2: BP4
Natera, Inc.	RCV000232038	SCV002088876	likely benign	Primary ciliary dyskinesia	2020-01-29	no assertion criteria provided	clinical testing