rs773466310
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS2
The NM_017841.4(SDHAF2):c.156G>A(p.Leu52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,862 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 Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SDHAF2
NM_017841.4 synonymous
NM_017841.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.12
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 -12 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 11-61437744-G-A is Benign according to our data. Variant chr11-61437744-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 463817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHAF2 | NM_017841.4 | c.156G>A | p.Leu52= | synonymous_variant | 2/4 | ENST00000301761.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHAF2 | ENST00000301761.7 | c.156G>A | p.Leu52= | synonymous_variant | 2/4 | 1 | NM_017841.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251320Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135826
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727234
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GnomAD4 genome ? Cov.: 32
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32
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Hereditary pheochromocytoma-paraganglioma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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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