rs752462796

Variant names:

• chr11-61437782-C-A
• rs752462796
• NM_017841.4:c.194C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-61437782-C-A
• chr11-61437782-C-G
• chr11-61437782-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017841.4(SDHAF2):​c.194C>A​(p.Thr65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T65S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDHAF2 NM_017841.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000256591 (HGNC:):

ACMG classification

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=0.31616104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF2	NM_017841.4	c.194C>A	p.Thr65Asn	missense_variant	Exon 2 of 4	ENST00000301761.7	NP_060311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF2	ENST00000301761.7	c.194C>A	p.Thr65Asn	missense_variant	Exon 2 of 4	1	NM_017841.4	ENSP00000301761.3
ENSG00000256591	ENST00000541135.5	c.194C>A	p.Thr65Asn	missense_variant	Exon 2 of 5	4		ENSP00000443130.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	.;T;.;.;.
Eigen	Benign	0.093
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;T;D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.0	.;M;.;.;.
PhyloP100		2.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;N;.;.;D
REVEL	Uncertain	0.32
Sift	Benign	0.044	D;D;.;.;D
Sift4G	Uncertain	0.060	T;T;D;D;D
Polyphen		0.83	.;P;.;.;.
Vest4		0.29, 0.28, 0.30, 0.30
MutPred		0.23		Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);Loss of phosphorylation at T65 (P = 0.0337);
MVP		0.50
MPC		0.20
ClinPred		0.78	D
GERP RS		5.3
Varity_R		0.59
gMVP		0.48
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs752462796; hg19: chr11-61205254;