Variant chr1-161210087-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377299.1(NDUFS2):c.703-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,610,726 control chromosomes in the GnomAD database, including 42,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.22 ( 3936 hom., cov: 31)

Exomes 𝑓: 0.23 ( 38789 hom. )

Consequence

NDUFS2
NM_001377299.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.24

Variant links:

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 links:

NDUFS2 (HGNC:):

NDUFS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-161210087-G-A is Benign according to our data. Variant chr1-161210087-G-A is described in ClinVar as [Benign]. Clinvar id is 1241229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS2	NM_001377299.1 linkuse as main transcript	c.703-24G>A		intron_variant		ENST00000676972.1	NP_001364228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000676972.1 linkuse as main transcript	c.703-24G>A		intron_variant			NM_001377299.1	ENSP00000503117.1		O75306-1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33822

AN:

151962

Hom.:

3928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.250

AC:

62934

AN:

251432

Hom.:

8486

AF XY:

0.249

AC XY:

33780

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.337

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.393

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.226

AC:

329674

AN:

1458646

Hom.:

38789

Cov.:

AF XY:

0.227

AC XY:

164947

AN XY:

725834

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.223

AC:

33860

AN:

152080

Hom.:

3936

Cov.:

AF XY:

0.225

AC XY:

16731

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.398

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.227

Hom.:

5656

Bravo

AF:

0.229

Asia WGS

AF:

0.337

AC:

1170

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.21

DANN

Benign

0.43

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over