rs10797094

Positions:

• chr1-161212882-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NDUFS2	NM_001377299.1	c.1116+402G>A		intron_variant		ENST00000676972.1	NP_001364228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000676972.1	c.1116+402G>A		intron_variant			NM_001377299.1	ENSP00000503117	P1

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

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.630

Alfa AF: 0.592 Hom.: 35101

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

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: rs10797094; hg19: chr1-161182672;