chr18-9117869-T-C

Position:

chr18-9117869-T-C

Variant summary

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

The ENST00000318388.11(NDUFV2):c.86T>C(p.Val29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,595,082 control chromosomes in the GnomAD database, including 525,894 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47701 hom., cov: 32)

Exomes 𝑓: 0.81 ( 478193 hom. )

Consequence

NDUFV2
ENST00000318388.11 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:9

Conservation

PhyloP100: 1.58

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.578213E-7).

BP6

Variant 18-9117869-T-C is Benign according to our data. Variant chr18-9117869-T-C is described in ClinVar as [Benign]. Clinvar id is 9054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-9117869-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NDUFV2	NM_021074.5 linkuse as main transcript	c.86T>C	p.Val29Ala	missense_variant	2/8	ENST00000318388.11	NP_066552.2
NDUFV2	XM_017025782.2 linkuse as main transcript	c.-2T>C		5_prime_UTR_variant	2/8		XP_016881271.1
NDUFV2	XR_243808.4 linkuse as main transcript	n.131T>C		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV2	ENST00000318388.11 linkuse as main transcript	c.86T>C	p.Val29Ala	missense_variant	2/8	1	NM_021074.5	ENSP00000327268	P1

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120110

AN:

152030

Hom.:

47658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.758

Gnomad ASJ

AF:

0.893

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.858

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.815

GnomAD3 exomes

AF:

0.798

AC:

200495

AN:

251114

Hom.:

80523

AF XY:

0.805

AC XY:

109345

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.757

Gnomad AMR exome

AF:

0.750

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

0.716

Gnomad SAS exome

AF:

0.859

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.816

Gnomad OTH exome

AF:

0.820

GnomAD4 exome

AF:

0.813

AC:

1172718

AN:

1442934

Hom.:

478193

Cov.:

AF XY:

0.815

AC XY:

585798

AN XY:

719068

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.752

Gnomad4 ASJ exome

AF:

0.896

Gnomad4 EAS exome

AF:

0.656

Gnomad4 SAS exome

AF:

0.862

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.819

Gnomad4 OTH exome

AF:

0.819

GnomAD4 genome

AF:

0.790

AC:

120207

AN:

152148

Hom.:

47701

Cov.:

AF XY:

0.787

AC XY:

58539

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.893

Gnomad4 EAS

AF:

0.713

Gnomad4 SAS

AF:

0.858

Gnomad4 FIN

AF:

0.745

Gnomad4 NFE

AF:

0.818

Gnomad4 OTH

AF:

0.812

Alfa

AF:

0.814

Hom.:

21804

Bravo

AF:

0.789

TwinsUK

AF:

0.815

AC:

3021

ALSPAC

AF:

0.831

AC:

3203

ESP6500AA

AF:

0.761

AC:

3352

ESP6500EA

AF:

0.819

AC:

7042

ExAC

AF:

0.800

AC:

97097

Asia WGS

AF:

0.720

AC:

2503

AN:

3478

EpiCase

AF:

0.818

EpiControl

AF:

0.824

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mitochondrial complex 1 deficiency, nuclear type 7

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 11, 2021	- -

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 03, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Parkinson disease, mitochondrial

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Apr 01, 1998

- -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.2

DANN

Benign

0.82

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.026

T;T

MetaRNN

Benign

7.6e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0

B;.

Vest4

0.070

MPC

0.040

ClinPred

0.0032

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.58

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