chr1-161202168-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000367993.7(NDUFS2):c.-218G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 604,890 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 4 hom. )
Consequence
NDUFS2
ENST00000367993.7 5_prime_UTR
ENST00000367993.7 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.386
Genes affected
NDUFS2 (HGNC:7708): (NADH:ubiquinone oxidoreductase core subunit S2) The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS2 | NM_001377298.1 | c.-218G>A | 5_prime_UTR_variant | 2/15 | |||
NDUFS2 | NM_001377300.1 | c.-218G>A | 5_prime_UTR_variant | 2/14 | |||
NDUFS2 | NM_001377301.1 | c.-218G>A | 5_prime_UTR_variant | 2/14 | |||
NDUFS2 | NM_004550.5 | c.-218G>A | 5_prime_UTR_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS2 | ENST00000367993.7 | c.-218G>A | 5_prime_UTR_variant | 2/15 | 1 | P1 | |||
NDUFS2 | ENST00000392179.5 | c.-218G>A | 5_prime_UTR_variant | 1/13 | 1 | ||||
NDUFS2 | ENST00000677231.1 | c.-218G>A | 5_prime_UTR_variant | 2/13 |
Frequencies
GnomAD3 genomes AF: 0.00165 AC: 251AN: 152178Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.00187 AC: 846AN: 452594Hom.: 4 Cov.: 4 AF XY: 0.00162 AC XY: 388AN XY: 239140
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GnomAD4 genome AF: 0.00165 AC: 251AN: 152296Hom.: 1 Cov.: 32 AF XY: 0.00156 AC XY: 116AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mitochondrial complex I deficiency, nuclear type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at