Submissions for variant NM_003114.5(SPAG1):c.2707G>A (p.Asp903Asn)

gnomAD frequency: 0.00021  dbSNP: rs148756457

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455105	SCV000540412	uncertain significance	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: PCD not consistent with patient phenotype, no second allele
Labcorp Genetics (formerly Invitae), Labcorp	RCV000803468	SCV000943340	uncertain significance	Primary ciliary dyskinesia 28	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 903 of the SPAG1 protein (p.Asp903Asn). This variant is present in population databases (rs148756457, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of SPAG1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 403466). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPAG1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV000803468	SCV001522921	uncertain significance	Primary ciliary dyskinesia 28	2019-09-06	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000803468	SCV001984675	uncertain significance	Primary ciliary dyskinesia 28	2020-11-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003168717	SCV003906632	uncertain significance	Primary ciliary dyskinesia	2023-02-10	criteria provided, single submitter	clinical testing	The p.D903N variant (also known as c.2707G>A), located in coding exon 18 of the SPAG1 gene, results from a G to A substitution at nucleotide position 2707. The aspartic acid at codon 903 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000803468	SCV005669605	uncertain significance	Primary ciliary dyskinesia 28	2024-06-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003392261	SCV004119156	uncertain significance	SPAG1-related disorder	2024-09-10	no assertion criteria provided	clinical testing	The SPAG1 c.2707G>A variant is predicted to result in the amino acid substitution p.Asp903Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.030% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.