GeneBe

rs868016844

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_017841.4(SDHAF2):​c.109G>A​(p.Gly37Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G37C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SDHAF2
NM_017841.4 missense

Scores

4
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Publications

0 publications found
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]
SDHAF2 Gene-Disease associations (from GenCC):
  • hereditary pheochromocytoma-paraganglioma
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • pheochromocytoma/paraganglioma syndrome 2
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36534724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017841.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SDHAF2
NM_017841.4
MANE Select
c.109G>Ap.Gly37Ser
missense
Exon 2 of 4NP_060311.1Q9NX18

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SDHAF2
ENST00000301761.7
TSL:1 MANE Select
c.109G>Ap.Gly37Ser
missense
Exon 2 of 4ENSP00000301761.3Q9NX18
ENSG00000256591
ENST00000541135.5
TSL:4
c.109G>Ap.Gly37Ser
missense
Exon 2 of 5ENSP00000443130.1F5H5T6
SDHAF2
ENST00000713963.1
c.202G>Ap.Gly68Ser
missense
Exon 3 of 5ENSP00000519256.1A0AAQ5BH90

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Hereditary pheochromocytoma-paraganglioma (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.017
T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.37
T
MetaSVM
Uncertain
0.030
D
MutationAssessor
Uncertain
2.8
M
PhyloP100
5.7
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.36
Sift
Benign
0.082
T
Sift4G
Benign
0.17
T
Polyphen
1.0
D
Vest4
0.41
MutPred
0.094
Gain of phosphorylation at G37 (P = 0.0172)
MVP
0.78
MPC
0.33
ClinPred
0.90
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.18
gMVP
0.44
Mutation Taster
=47/53
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs868016844; hg19: chr11-61205169; API