rs879647

chr11-61437962-G-Achr11-61437962-G-Cchr11-61437962-G-T

Variant summary

Our verdict is Benign. Variant got -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:3
• Conservation: PhyloP100: 0.538

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 260942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61437962-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDHAF2	NM_017841.4	c.261-42G>A		intron_variant		ENST00000301761.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDHAF2	ENST00000301761.7	c.261-42G>A		intron_variant		1	NM_017841.4	P1

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

GnomAD3 exomes AF: 0.831 AC: 206178 AN: 248050 Hom.: 87871 AF XY: 0.838 AC XY: 112848 AN XY: 134590

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 SAS exome AF: 0.833

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

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.971

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.880

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.830

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.764

Alfa AF: 0.792 Hom.: 9995

Bravo AF: 0.701

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Paragangliomas 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.7
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

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