Variant 5-60945315-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_174889.5(NDUFAF2):c.60G>A(p.Lys20Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,547,454 control chromosomes in the GnomAD database, including 241,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31127 hom., cov: 31)

Exomes 𝑓: 0.58 ( 210605 hom. )

Consequence

NDUFAF2
NM_174889.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.915

Variant links:

Genes affected

NDUFAF2 (HGNC:28086): (NADH:ubiquinone oxidoreductase complex assembly factor 2) NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. This gene encodes a complex I assembly factor. Mutations in this gene cause progressive encephalopathy resulting from mitochondrial complex I deficiency. [provided by RefSeq, Jul 2008]

NDUFAF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 5-60945315-G-A is Benign according to our data. Variant chr5-60945315-G-A is described in ClinVar as [Benign]. Clinvar id is 129691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-60945315-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.915 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF2	NM_174889.5 link	c.60G>A	p.Lys20Lys	synonymous_variant	Exon 1 of 4	ENST00000296597.10	NP_777549.1	Q8N183A0A0S2Z5U1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF2	ENST00000296597.10 link	c.60G>A	p.Lys20Lys	synonymous_variant	Exon 1 of 4	1	NM_174889.5	ENSP00000296597.5		Q8N183

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96496

AN:

151810

Hom.:

31099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.823

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.944

Gnomad SAS

AF:

0.671

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.619

GnomAD3 exomes

AF:

0.650

AC:

159574

AN:

245620

Hom.:

52304

AF XY:

0.644

AC XY:

85508

AN XY:

132758

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.753

Gnomad ASJ exome

AF:

0.570

Gnomad EAS exome

AF:

0.939

Gnomad SAS exome

AF:

0.658

Gnomad FIN exome

AF:

0.593

Gnomad NFE exome

AF:

0.594

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.576

AC:

803812

AN:

1395526

Hom.:

210605

Cov.:

AF XY:

0.578

AC XY:

402838

AN XY:

696378

show subpopulations

Gnomad4 AFR exome

AF:

0.589

Gnomad4 AMR exome

AF:

0.740

Gnomad4 ASJ exome

AF:

0.550

Gnomad4 EAS exome

AF:

0.933

Gnomad4 SAS exome

AF:

0.638

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.549

Gnomad4 OTH exome

AF:

0.588

GnomAD4 genome

AF:

0.636

AC:

96567

AN:

151928

Hom.:

31127

Cov.:

AF XY:

0.639

AC XY:

47458

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.628

Gnomad4 AMR

AF:

0.683

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.943

Gnomad4 SAS

AF:

0.671

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.622

Alfa

AF:

0.606

Hom.:

9594

Bravo

AF:

0.641

Asia WGS

AF:

0.818

AC:

2845

AN:

3478

EpiCase

AF:

0.600

EpiControl

AF:

0.597

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

Leigh syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Cockayne syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial complex 1 deficiency, nuclear type 10

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

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