chr1-161201946-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000367993.7(NDUFS2):c.-239-201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 216,784 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.015 ( 29 hom., cov: 32)
Exomes 𝑓: 0.013 ( 13 hom. )
Consequence
NDUFS2
ENST00000367993.7 intron
ENST00000367993.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.194
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 1-161201946-A-G is Benign according to our data. Variant chr1-161201946-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1207148.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2292/152306) while in subpopulation NFE AF= 0.0213 (1448/68020). AF 95% confidence interval is 0.0204. There are 29 homozygotes in gnomad4. There are 1201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 29 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS2 | NM_001377298.1 | c.-239-201A>G | intron_variant | ||||
NDUFS2 | NM_001377300.1 | c.-239-201A>G | intron_variant | ||||
NDUFS2 | NM_001377301.1 | c.-239-201A>G | intron_variant | ||||
NDUFS2 | NM_004550.5 | c.-239-201A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS2 | ENST00000367993.7 | c.-239-201A>G | intron_variant | 1 | P1 | ||||
NDUFS2 | ENST00000676600.1 | c.-76-364A>G | intron_variant | P1 | |||||
NDUFS2 | ENST00000677231.1 | c.-239-201A>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0151 AC: 2293AN: 152188Hom.: 29 Cov.: 32
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GnomAD4 exome AF: 0.0134 AC: 861AN: 64478Hom.: 13 AF XY: 0.0122 AC XY: 427AN XY: 35116
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GnomAD4 genome ? AF: 0.0150 AC: 2292AN: 152306Hom.: 29 Cov.: 32 AF XY: 0.0161 AC XY: 1201AN XY: 74480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at