Submissions for variant NM_001038.6(SCNN1A):c.-55+2T>C

gnomAD frequency: 0.00122  dbSNP: rs772498945

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000779114	SCV000915608	uncertain significance	Pseudohypoaldosteronism, type IB1, autosomal recessive	2018-12-08	criteria provided, single submitter	clinical testing	The SCNN1A c.-55+2T>C variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The variant is reported at a frequency of 0.001693 in the European (non-Finnish) population from the Genome Aggregation Database. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for pseudohypoaldosteronism, type I, recessive. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Illumina Laboratory Services, Illumina	RCV001114923	SCV001272846	benign	Bronchiectasis with or without elevated sweat chloride 2	2017-11-20	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV000722903	SCV001774165	uncertain significance	not provided	2019-07-31	criteria provided, single submitter	clinical testing	In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Gharavi Laboratory, Columbia University	RCV000722903	SCV000854034	uncertain significance	not provided	2018-09-16	no assertion criteria provided	research