Genetic Variant NDUFV2:c.54+6689T>G (chr18-9109486-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021074.5(NDUFV2):c.54+6689T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,108 control chromosomes in the GnomAD database, including 30,678 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 ( 30678 hom., cov: 32)

Consequence

NDUFV2
NM_021074.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.228

Publications

13 publications found

Variant links:

Genes affected

NDUFV2 (HGNC:7717): (NADH:ubiquinone oxidoreductase core subunit V2) The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes the 24 kDa subunit of complex I, and is involved in electron transfer. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy. A non-transcribed pseudogene of this locus is found on chromosome 19. [provided by RefSeq, Oct 2009]

NDUFV2 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial complex I deficiency, nuclear type 7
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

NDUFV2 links:

ENSG00000265257 (HGNC:):

ENSG00000265257 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFV2	NM_021074.5 link	c.54+6689T>G		intron_variant	Intron 1 of 7	ENST00000318388.11	NP_066552.2	P19404
NDUFV2	XR_243808.4 link	n.99+6689T>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFV2	ENST00000318388.11 link	c.54+6689T>G		intron_variant	Intron 1 of 7	1	NM_021074.5	ENSP00000327268.6		P19404

Frequencies

GnomAD3 genomes

AF:

0.623

AC:

94616

AN:

151990

Hom.:

30668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.697

Gnomad SAS

AF:

0.784

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.654

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

GnomAD4 genome

AF:

0.622

AC:

94659

AN:

152108

Hom.:

30678

Cov.:

AF XY:

0.627

AC XY:

46646

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.425

AC:

17636

AN:

41462

American (AMR)

AF:

0.655

AC:

10013

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2616

AN:

3472

East Asian (EAS)

AF:

0.696

AC:

3603

AN:

5174

South Asian (SAS)

AF:

0.786

AC:

3794

AN:

4828

European-Finnish (FIN)

AF:

0.696

AC:

7377

AN:

10596

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.697

AC:

47349

AN:

67976

Other (OTH)

AF:

0.650

AC:

1375

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1754

3508

5262

7016

8770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.678

Hom.:

58800

Bravo

AF:

0.611

Asia WGS

AF:

0.648

AC:

2252

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.3

(source)

DANN

Benign

0.74

PhyloP100

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over