NM_017841.4:c.341A>G
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_017841.4(SDHAF2):c.341A>G(p.Asn114Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,980 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
Consequence
NM_017841.4 missense
Scores
Clinical Significance
Conservation
Publications
- hereditary pheochromocytoma-paragangliomaInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- pheochromocytoma/paraganglioma syndrome 2Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHAF2 | ENST00000301761.7 | c.341A>G | p.Asn114Ser | missense_variant | Exon 3 of 4 | 1 | NM_017841.4 | ENSP00000301761.3 | ||
ENSG00000256591 | ENST00000541135.5 | c.341A>G | p.Asn114Ser | missense_variant | Exon 3 of 5 | 4 | ENSP00000443130.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000437 AC: 11AN: 251492 AF XY: 0.0000515 show subpopulations
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461678Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727156 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74474 show subpopulations
ClinVar
Submissions by phenotype
Hereditary pheochromocytoma-paraganglioma Uncertain:2
This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 114 of the SDHAF2 protein (p.Asn114Ser). This variant is present in population databases (rs747022200, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 575138). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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Pheochromocytoma/paraganglioma syndrome 2 Uncertain:1
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Hereditary cancer-predisposing syndrome Uncertain:1
The p.N114S variant (also known as c.341A>G), located in coding exon 3 of the SDHAF2 gene, results from an A to G substitution at nucleotide position 341. The asparagine at codon 114 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Ovarian cancer Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at