chr18-9109486-T-G

Variant names:

• chr18-9109486-T-G
• rs4148965
• NM_021074.5:c.54+6689T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 13 publications found

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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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

ENSG00000265257 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021074.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV2	NM_021074.5	MANE Select	c.54+6689T>G		intron	N/A	NP_066552.2	P19404

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV2	ENST00000318388.11	TSL:1 MANE Select	c.54+6689T>G		intron	N/A	ENSP00000327268.6	P19404
	NDUFV2	ENST00000860027.1		c.54+6689T>G		intron	N/A	ENSP00000530086.1
	NDUFV2	ENST00000400033.1	TSL:3	c.63+4507T>G		intron	N/A	ENSP00000382908.1	E7EPT4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94616 AN: 151990 Hom.: 30668 Cov.: 32

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.: 32 AF XY: 0.627 AC XY: 46646 AN XY: 74374

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
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)

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

Other links and lift over

dbSNP: rs4148965; hg19: chr18-9109484;