chr18-9119037-T-G

Variant names:

• chr18-9119037-T-G
• rs977581
• NM_021074.5:c.121-289T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021074.5(NDUFV2):​c.121-289T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,826 control chromosomes in the GnomAD database, including 23,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (23074 hom., cov: 29)
• Consequence: NDUFV2 NM_021074.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-9119037-T-G is Benign according to our data. Variant chr18-9119037-T-G is described in ClinVar as Benign. ClinVar VariationId is 669520.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 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.121-289T>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.121-289T>G		intron	N/A	ENSP00000327268.6	P19404
	NDUFV2	ENST00000860027.1		c.121-289T>G		intron	N/A	ENSP00000530086.1
	NDUFV2	ENST00000400033.1	TSL:3	c.130-289T>G		intron	N/A	ENSP00000382908.1	E7EPT4

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79319 AN: 151708 Hom.: 23072 Cov.: 29

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.523 AC: 79334 AN: 151826 Hom.: 23074 Cov.: 29 AF XY: 0.531 AC XY: 39354 AN XY: 74174

African (AFR) AF: 0.245 AC: 10174 AN: 41462

American (AMR) AF: 0.597 AC: 9115 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2276 AN: 3458

East Asian (EAS) AF: 0.672 AC: 3475 AN: 5170

South Asian (SAS) AF: 0.746 AC: 3583 AN: 4802

European-Finnish (FIN) AF: 0.637 AC: 6682 AN: 10488

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.619 AC: 42014 AN: 67870

Other (OTH) AF: 0.572 AC: 1205 AN: 2108

Alfa AF: 0.596 Hom.: 13260

Bravo AF: 0.508

Asia WGS AF: 0.603 AC: 2091 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.70
PhyloP100		1.3
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: rs977581; hg19: chr18-9119035;