18-9102782-C-G

Variant names:

• chr18-9102782-C-G
• rs1368727243
• NM_021074.5:c.39C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021074.5(NDUFV2):​c.39C>G​(p.Gly13Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDUFV2 NM_021074.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.693
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 18-9102782-C-G is Benign according to our data. Variant chr18-9102782-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1911157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.693 with no splicing effect.

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.39C>G	p.Gly13Gly	synonymous	Exon 1 of 8	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.39C>G	p.Gly13Gly	synonymous	Exon 1 of 8	ENSP00000327268.6	P19404
	NDUFV2	ENST00000860027.1		c.39C>G	p.Gly13Gly	synonymous	Exon 1 of 8	ENSP00000530086.1
	NDUFV2	ENST00000860025.1		c.39C>G	p.Gly13Gly	synonymous	Exon 1 of 8	ENSP00000530084.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1425160 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705872

African (AFR) AF: 0.00 AC: 0 AN: 32408

American (AMR) AF: 0.00 AC: 0 AN: 39566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 37804

South Asian (SAS) AF: 0.00 AC: 0 AN: 81400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095904

Other (OTH) AF: 0.00 AC: 0 AN: 58882

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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	-0.76
CADD	Benign	11
DANN	Benign	0.53
PhyloP100		0.69
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs1368727243; hg19: chr18-9102780;