rs41274300

Positions:

chr18-9119491-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021074.5(NDUFV2):c.201A>T(p.Val67Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,613,072 control chromosomes in the GnomAD database, including 9,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1072 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8677 hom. )

Consequence

NDUFV2
NM_021074.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.26

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:

ENSG00000265257 (HGNC:):

ENSG00000265257 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 18-9119491-A-T is Benign according to our data. Variant chr18-9119491-A-T is described in ClinVar as [Benign]. Clinvar id is 129703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFV2	NM_021074.5 link	c.201A>T	p.Val67Val	synonymous_variant	4/8	ENST00000318388.11	NP_066552.2	P19404
NDUFV2	XM_017025782.2 link	c.114A>T	p.Val38Val	synonymous_variant	4/8		XP_016881271.1
NDUFV2	XR_243808.4 link	n.246A>T		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV2	ENST00000318388.11 link	c.201A>T	p.Val67Val	synonymous_variant	4/8	1	NM_021074.5	ENSP00000327268.6		P19404

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16624

AN:

152184

Hom.:

1069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0799

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0538

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.0831

AC:

20847

AN:

250820

Hom.:

1143

AF XY:

0.0833

AC XY:

11308

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0505

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0598

Gnomad FIN exome

AF:

0.0379

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.0906

GnomAD4 exome

AF:

0.103

AC:

151094

AN:

1460770

Hom.:

8677

Cov.:

AF XY:

0.102

AC XY:

74255

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0529

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0626

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.109

AC:

16626

AN:

152302

Hom.:

1072

Cov.:

AF XY:

0.103

AC XY:

7706

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0797

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0530

Gnomad4 FIN

AF:

0.0363

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.111

Hom.:

349

Bravo

AF:

0.114

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.118

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Mitochondrial complex 1 deficiency, nuclear type 7

Benign:2

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	- -

not specified

Benign:1

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. -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.2

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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