chr18-9103048-GATAT-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021074.5(NDUFV2):​c.54+262_54+265delATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 321,560 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000031 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NDUFV2
NM_021074.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDUFV2NM_021074.5 linkc.54+262_54+265delATAT intron_variant Intron 1 of 7 ENST00000318388.11 NP_066552.2 P19404
NDUFV2XR_243808.4 linkn.99+262_99+265delATAT intron_variant Intron 1 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDUFV2ENST00000318388.11 linkc.54+262_54+265delATAT intron_variant Intron 1 of 7 1 NM_021074.5 ENSP00000327268.6 P19404

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
151252
Hom.:
0
Cov.:
32
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
4906
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000311
AC:
1
AN:
321560
Hom.:
0
AF XY:
0.00000598
AC XY:
1
AN XY:
167278
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
7268
American (AMR)
AF:
0.00
AC:
0
AN:
9422
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10570
East Asian (EAS)
AF:
0.00
AC:
0
AN:
22756
South Asian (SAS)
AF:
0.0000412
AC:
1
AN:
24260
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25638
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1546
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
200126
Other (OTH)
AF:
0.00
AC:
0
AN:
19974
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
151252
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73794
African (AFR)
AF:
0.00
AC:
0
AN:
41236
American (AMR)
AF:
0.00
AC:
0
AN:
15194
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3456
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5166
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4806
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67704
Other (OTH)
AF:
0.00
AC:
0
AN:
2066

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.064

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs148124234; hg19: chr18-9103046; API