11-61437744-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017841.4(SDHAF2):​c.156G>T​(p.Leu52Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SDHAF2
NM_017841.4 missense

Scores

2
14
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDHAF2NM_017841.4 linkc.156G>T p.Leu52Phe missense_variant Exon 2 of 4 ENST00000301761.7 NP_060311.1 Q9NX18

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDHAF2ENST00000301761.7 linkc.156G>T p.Leu52Phe missense_variant Exon 2 of 4 1 NM_017841.4 ENSP00000301761.3 Q9NX18
ENSG00000256591ENST00000541135.5 linkc.156G>T p.Leu52Phe missense_variant Exon 2 of 5 4 ENSP00000443130.1 F5H5T6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461862
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1
Oct 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.L52F variant (also known as c.156G>T), located in coding exon 2 of the SDHAF2 gene, results from a G to T substitution at nucleotide position 156. The leucine at codon 52 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;T;.;.;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
D;D;D;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.36
T;T;T;T;T
MetaSVM
Uncertain
0.19
D
MutationAssessor
Uncertain
2.7
.;M;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.6
D;D;.;.;N
REVEL
Uncertain
0.51
Sift
Uncertain
0.021
D;D;.;.;D
Sift4G
Uncertain
0.010
D;D;D;D;D
Polyphen
1.0
.;D;.;.;.
Vest4
0.57, 0.58, 0.60, 0.72
MutPred
0.13
Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);
MVP
0.66
MPC
0.73
ClinPred
0.97
D
GERP RS
3.0
Varity_R
0.62
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.32
Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-61205216; COSMIC: COSV57099152; COSMIC: COSV57099152; API