Submissions for variant NM_001089.3(ABCA3):c.2119C>T (p.Leu707Phe)

gnomAD frequency: 0.00092  dbSNP: rs147341939

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000299658	SCV000396002	likely benign	Interstitial lung disease due to ABCA3 deficiency	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000927189	SCV001072768	likely benign	not provided	2024-03-06	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000299658	SCV001430647	likely benign	Interstitial lung disease due to ABCA3 deficiency	2020-06-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002418169	SCV002727074	uncertain significance	Hereditary pulmonary alveolar proteinosis	2015-03-06	criteria provided, single submitter	clinical testing	The p.L707F variant (also known as c.2119C>T), located in coding exon 14 of the ABCA3 gene, results from a C to T substitution at nucleotide position 2119. The leucine at codon 707 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs147341939. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.1% (2/2098) total alleles studied. The highest observed frequency was 0.94% (1/106) African-American SW alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.12% (16/12996) total alleles studied, having been observed in 0.36% (16/4396) African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.