rs113652589

Variant names:

• chr11-61446083-C-T
• rs113652589
• NM_017841.4:c.*12C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017841.4(SDHAF2):​c.*12C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,614,080 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (61 hom.)
• Consequence: SDHAF2 NM_017841.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -0.734
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000256591 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-61446083-C-T is Benign according to our data. Variant chr11-61446083-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00592 (902/152318) while in subpopulation NFE AF = 0.0101 (684/68036). AF 95% confidence interval is 0.00943. There are 1 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 902 AD gene.

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF2	NM_017841.4	MANE Select	c.*12C>T		3_prime_UTR	Exon 4 of 4	NP_060311.1	Q9NX18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF2	ENST00000301761.7	TSL:1 MANE Select	c.*12C>T		3_prime_UTR	Exon 4 of 4	ENSP00000301761.3	Q9NX18
	ENSG00000256591	ENST00000541135.5	TSL:4	c.377+7963C>T		intron	N/A	ENSP00000443130.1	F5H5T6
	SDHAF2	ENST00000713963.1		c.*12C>T		3_prime_UTR	Exon 5 of 5	ENSP00000519256.1	A0AAQ5BH90

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 901 AN: 152200 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00511 AC: 1284 AN: 251416 AF XY: 0.00519

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00938

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00783 AC: 11450 AN: 1461762 Hom.: 61 Cov.: 31 AF XY: 0.00756 AC XY: 5494 AN XY: 727198

African (AFR) AF: 0.00119 AC: 40 AN: 33480

American (AMR) AF: 0.00264 AC: 118 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00189 AC: 163 AN: 86256

European-Finnish (FIN) AF: 0.00199 AC: 106 AN: 53368

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.00957 AC: 10638 AN: 1111946

Other (OTH) AF: 0.00614 AC: 371 AN: 60390

GnomAD4 genome AF: 0.00592 AC: 902 AN: 152318 Hom.: 1 Cov.: 33 AF XY: 0.00513 AC XY: 382 AN XY: 74488

African (AFR) AF: 0.00156 AC: 65 AN: 41560

American (AMR) AF: 0.00451 AC: 69 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0101 AC: 684 AN: 68036

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00705 Hom.: 0

Bravo AF: 0.00603

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	-	2	not specified (2)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Hereditary pheochromocytoma-paraganglioma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.60
PhyloP100		-0.73
Mutation Taster		=100/0	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: rs113652589; hg19: chr11-61213555;