rs10797094

Variant names:

• chr1-161212882-G-A
• rs10797094
• NM_001377299.1:c.1116+402G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377299.1(NDUFS2):​c.1116+402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,928 control chromosomes in the GnomAD database, including 29,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29958 hom., cov: 31)
• Consequence: NDUFS2 NM_001377299.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 16 publications found

Genes affected

NDUFS2 (HGNC:7708): (NADH:ubiquinone oxidoreductase core subunit S2) The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

NDUFS2 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency, nuclear type 6

  Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome with cardiomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFS2	NM_001377299.1	c.1116+402G>A		intron_variant	Intron 10 of 13	ENST00000676972.1	NP_001364228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000676972.1	c.1116+402G>A		intron_variant	Intron 10 of 13		NM_001377299.1	ENSP00000503117.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94632 AN: 151810 Hom.: 29908 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.624 AC: 94732 AN: 151928 Hom.: 29958 Cov.: 31 AF XY: 0.628 AC XY: 46653 AN XY: 74256

African (AFR) AF: 0.656 AC: 27180 AN: 41426

American (AMR) AF: 0.683 AC: 10437 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2092 AN: 3470

East Asian (EAS) AF: 0.891 AC: 4607 AN: 5168

South Asian (SAS) AF: 0.746 AC: 3593 AN: 4818

European-Finnish (FIN) AF: 0.579 AC: 6097 AN: 10524

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.570 AC: 38738 AN: 67942

Other (OTH) AF: 0.630 AC: 1322 AN: 2100

Alfa AF: 0.596 Hom.: 45277

Bravo AF: 0.638

Asia WGS AF: 0.820 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.33
PhyloP100		-1.0
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: rs10797094; hg19: chr1-161182672;