rs16832694

Positions:

• chr1-161207016-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377299.1(NDUFS2):​c.393+419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,278 control chromosomes in the GnomAD database, including 445 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 0.072 (445 hom., cov: 31)
• Consequence: NDUFS2 NM_001377299.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS2	NM_001377299.1	c.393+419A>G		intron_variant		ENST00000676972.1	NP_001364228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000676972.1	c.393+419A>G		intron_variant			NM_001377299.1	ENSP00000503117.1

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10890 AN: 152160 Hom.: 439 Cov.: 31

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0718 AC: 10926 AN: 152278 Hom.: 445 Cov.: 31 AF XY: 0.0731 AC XY: 5447 AN XY: 74464

Gnomad4 AFR AF: 0.0638

Gnomad4 AMR AF: 0.0739

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.0705

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0641

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0711 Hom.: 74

Bravo AF: 0.0688

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.66
DANN	Benign	0.84

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: rs16832694; hg19: chr1-161176806;