11-61430146-A-C
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_017841.4(SDHAF2):c.-1A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
SDHAF2
NM_017841.4 5_prime_UTR
NM_017841.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.983
Genes affected
SDHAF2 (HGNC:26034): (succinate dehydrogenase complex assembly factor 2) This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 11-61430146-A-C is Benign according to our data. Variant chr11-61430146-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 392110.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250658Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135616
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727218
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 20, 2023 | See Variant Classification Assertion Criteria. - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2023 | The c.-1A>C variant is located in the 5' untranslated region (5’ UTR) of the SDHAF2 gene. This variant results from an A to C substitution 1 nucleotide upstream from the first translated codon. This nucleotide position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 30, 2024 | This variant is located in the 5' untranslated region of the SDHAF2 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHAF2-related disorders in the literature. This variant has been identified in 4/250658 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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