ClinVar Miner

Submissions for variant NM_001089.3(ABCA3):c.863G>A (p.Arg288Lys) (rs117603931)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000219053 SCV000269961 likely benign not specified 2015-01-15 criteria provided, single submitter clinical testing p.Arg288Lys in exon 8 of ABCA3: This variant is not expected to have clinical si gnificance because it has been identified in 0.95% (642/67532) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs117603931). In addition, multiple mammals (>10) carry a lysine (Lys) a t this position, supporting that this change is tolerated. While this variant ha s been reported in 2 individuals with pulmonary disease (Brasch 2006, Copertino 2012), its frequency in the general population and presence of the variant amino acid in multiple mammals supports that this variant is not likely a primary cau se of disease.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514255 SCV000609652 likely benign not provided 2017-02-27 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000850152 SCV000992326 uncertain significance Surfactant metabolism dysfunction, pulmonary, 3 2019-09-24 criteria provided, single submitter clinical testing This ABCA3 variant (rs117603931) reaches polymorphic frequency (greater or equal than 1%) within the European (non-Finnish) subpopulation in large population datasets (gnomAD: 1324/129014 total alleles; 1.03%; 11 homozygotes). Two submitters in ClinVar classify this variant as likely benign. This variant was previously reported as a potential disease-associated variant, however, in both cases it was located on the same chromosome (in cis) as a second, likely more deleterious ABCA3 variant. Two bioinformatic tools queried predict that this substitution would be tolerated, and the arginine residue at this position is not evolutionarily conserved across the species assessed. Multiple studies suggest that this variant may impact the function of ABCA3. Per our review and consultation with a clinical expert, this variant may contribute to an increased risk of neonatal respiratory distress in combination with other genetic and environmental factors. The clinical significance of c.863G>A is uncertain at this time.
Invitae RCV000514255 SCV001037379 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000850152 SCV001273222 uncertain significance Surfactant metabolism dysfunction, pulmonary, 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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