Submissions for variant NM_174889.5(NDUFAF2):c.451G>A (p.Gly151Ser)

gnomAD frequency: 0.00369  dbSNP: rs9885480

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000585479	SCV000693174	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	NDUFAF2: BP4, BS2
GeneDx	RCV000602804	SCV000729253	benign	not specified	2018-02-22	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000585479	SCV000884220	likely benign	not provided	2018-02-18	criteria provided, single submitter	clinical testing	The NDUFAF2 c.451G>A; p.Gly151Ser variant (rs9885480), to our knowledge, is not reported in the medical literature or gene specific variant databases. However, this variant is found in the Finnish European population with an allele frequency of 2.2% (580/25,694 alleles, including 5 homozygotes) in the Genome Aggregation Database. The glycine at codon 151 is highly conserved considering 11 species up to Tetraodon (Alamut software v2.10.0), but computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: possibly damaging). Based on the available evidence, the p.Gly151Ser variant is classified as likely benign.
Invitae	RCV000585479	SCV001023708	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001152463	SCV001313679	uncertain significance	Mitochondrial complex I deficiency, nuclear type 1	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV001153733	SCV001315036	likely benign	Leigh syndrome	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000585479	SCV001742483	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000585479	SCV001973713	likely benign	not provided		no assertion criteria provided	clinical testing