Submissions for variant NM_004168.4(SDHA):c.150+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1057523165

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000438780	SCV000530955	uncertain significance	not provided	2023-09-11	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame deletion of exon 2; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000471142	SCV000553900	likely pathogenic	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 2 of the SDHA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of SDHA-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 388610). Studies have shown that disruption of this splice site results in skipping of exon 2, but is expected to preserve the integrity of the reading-frame (Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics	RCV000568947	SCV000674982	likely pathogenic	Hereditary cancer-predisposing syndrome	2024-04-29	criteria provided, single submitter	clinical testing	The c.150+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 2 of the SDHA gene. This variant has been observed in individuals with a personal and/or family history that is consistent with SDHA-associated disease (Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Baylor Genetics	RCV003476016	SCV004200639	likely pathogenic	Dilated cardiomyopathy 1GG	2023-05-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000438780	SCV001809661	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000438780	SCV001959988	likely pathogenic	not provided		no assertion criteria provided	clinical testing