11-61430143-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_017841.4(SDHAF2):c.-4G>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 0.0000118 in 1,614,108 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
SDHAF2
NM_017841.4 5_prime_UTR
NM_017841.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.97
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 11-61430143-G-A is Benign according to our data. Variant chr11-61430143-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2560489.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHAF2 | NM_017841.4 | c.-4G>A | 5_prime_UTR_variant | 1/4 | ENST00000301761.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHAF2 | ENST00000301761.7 | c.-4G>A | 5_prime_UTR_variant | 1/4 | 1 | NM_017841.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250578Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135572
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727210
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2023 | The c.-4G>A variant is located in the 5' untranslated region (5’ UTR) of the SDHAF2 gene. This variant results from a G to A substitution 4 bases upstream from the first translated codon. This nucleotide position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
SDHAF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 27, 2022 | 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). - |
Computational scores
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BayesDel_noAF
Benign
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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