rs879647

Variant names:

• chr11-61437962-G-A
• rs879647
• NM_017841.4:c.261-42G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-61437962-G-A
• chr11-61437962-G-C
• chr11-61437962-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017841.4(SDHAF2):​c.261-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 1,591,444 control chromosomes in the GnomAD database, including 553,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (43194 hom., cov: 30)
  • Exomes 𝑓: 0.84 (510519 hom.)
• Consequence: SDHAF2 NM_017841.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.538
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-61437962-G-A is Benign according to our data. Variant chr11-61437962-G-A is described in ClinVar as Benign. ClinVar VariationId is 260942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF2	NM_017841.4	MANE Select	c.261-42G>A		intron	N/A	NP_060311.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF2	ENST00000301761.7	TSL:1 MANE Select	c.261-42G>A		intron	N/A	ENSP00000301761.3
	ENSG00000256591	ENST00000541135.5	TSL:4	c.261-42G>A		intron	N/A	ENSP00000443130.1
	SDHAF2	ENST00000713963.1		c.354-42G>A		intron	N/A	ENSP00000519256.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109469 AN: 151834 Hom.: 43197 Cov.: 30

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.769

GnomAD2 exomes AF: 0.831 AC: 206178 AN: 248050 AF XY: 0.838

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.889

Gnomad EAS exome AF: 0.963

Gnomad FIN exome AF: 0.880

Gnomad NFE exome AF: 0.851

Gnomad OTH exome AF: 0.852

GnomAD4 exome AF: 0.838 AC: 1206160 AN: 1439492 Hom.: 510519 Cov.: 26 AF XY: 0.840 AC XY: 602715 AN XY: 717536

African (AFR) AF: 0.345 AC: 11344 AN: 32926

American (AMR) AF: 0.860 AC: 38379 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 23043 AN: 25990

East Asian (EAS) AF: 0.971 AC: 38447 AN: 39610

South Asian (SAS) AF: 0.836 AC: 71724 AN: 85754

European-Finnish (FIN) AF: 0.880 AC: 46622 AN: 52982

Middle Eastern (MID) AF: 0.857 AC: 4413 AN: 5152

European-Non Finnish (NFE) AF: 0.844 AC: 922755 AN: 1092858

Other (OTH) AF: 0.830 AC: 49433 AN: 59580

GnomAD4 genome AF: 0.720 AC: 109479 AN: 151952 Hom.: 43194 Cov.: 30 AF XY: 0.728 AC XY: 54057 AN XY: 74292

African (AFR) AF: 0.366 AC: 15135 AN: 41376

American (AMR) AF: 0.824 AC: 12588 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3094 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5014 AN: 5164

South Asian (SAS) AF: 0.819 AC: 3928 AN: 4798

European-Finnish (FIN) AF: 0.884 AC: 9345 AN: 10576

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57680 AN: 67982

Other (OTH) AF: 0.764 AC: 1611 AN: 2110

Alfa AF: 0.781 Hom.: 10046

Bravo AF: 0.701

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pheochromocytoma/paraganglioma syndrome 2 Benign:2

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.49
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs879647; hg19: chr11-61205434; COSMIC: COSV57099875; COSMIC: COSV57099875;