Submissions for variant NM_003114.5(SPAG1):c.2367del (p.Ser789fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003741037	SCV004551708	pathogenic	Primary ciliary dyskinesia 28	2024-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser789Argfs*12) in the SPAG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPAG1 are known to be pathogenic (PMID: 24055112). This variant is present in population databases (rs757398573, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SPAG1-related conditions. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004756545	SCV005349236	likely pathogenic	SPAG1-related disorder	2024-08-15	no assertion criteria provided	clinical testing	The SPAG1 c.2367delC variant is predicted to result in a frameshift and premature protein termination (p.Ser789Argfs*12). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in SPAG1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.