18-9119037-T-G

Position:

• chr18-9119037-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFV2	NM_021074.5	c.121-289T>G		intron_variant		ENST00000318388.11
NDUFV2	XM_017025782.2	c.34-289T>G		intron_variant
NDUFV2	XR_243808.4	n.166-289T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFV2	ENST00000318388.11	c.121-289T>G		intron_variant		1	NM_021074.5	P1
NDUFV2	ENST00000400033.1	c.130-289T>G		intron_variant		3
NDUFV2	ENST00000474350.5	n.518-289T>G		intron_variant, non_coding_transcript_variant		3
NDUFV2	ENST00000483511.1	n.180-289T>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.572

Alfa AF: 0.600 Hom.: 11808

Bravo AF: 0.508

Asia WGS AF: 0.603 AC: 2091 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs977581; hg19: chr18-9119035;