Submissions for variant NM_001377299.1(NDUFS2):c.1354+5G>A

gnomAD frequency: 0.00042  dbSNP: rs190184430

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127152	SCV000170706	benign	not specified	2014-06-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000275644	SCV000350138	uncertain significance	Mitochondrial complex I deficiency, nuclear type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001303885	SCV001493150	uncertain significance	not provided	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change falls in intron 14 of the NDUFS2 gene. It does not directly change the encoded amino acid sequence of the NDUFS2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs190184430, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with NDUFS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 138487). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001303885	SCV002821441	uncertain significance	not provided	2022-10-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965059	SCV004784652	likely benign	NDUFS2-related disorder	2020-05-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV001303885	SCV002585008	not provided	not provided		no assertion provided	research