11-78069876-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004549.6(NDUFC2):c.*111G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,607,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (0 hom.)
• Consequence: NDUFC2 NM_004549.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.772

Genes affected

NDUFC2 (HGNC:7706): (NADH:ubiquinone oxidoreductase subunit C2) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency. [provided by Alliance of Genome Resources, Apr 2022]

NDUFC2-KCTD14 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-78069876-C-T is Benign according to our data. Variant chr11-78069876-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642196.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFC2	NM_004549.6	c.*111G>A		3_prime_UTR_variant	3/3	ENST00000281031.5
NDUFC2-KCTD14	NM_001203262.2	c.166+9703G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFC2	ENST00000281031.5	c.*111G>A		3_prime_UTR_variant	3/3	1	NM_004549.6	P1
NDUFC2	ENST00000527806.1	c.264G>A	p.Leu88=	synonymous_variant	3/3	2
NDUFC2	ENST00000525085.1	c.*111G>A		3_prime_UTR_variant	3/3	3
NDUFC2	ENST00000534029.5	c.*111G>A		3_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000425 AC: 103 AN: 242460 Hom.: 0 AF XY: 0.000397 AC XY: 52 AN XY: 131090

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.000845

Gnomad OTH exome AF: 0.000671

GnomAD4 exome AF: 0.000528 AC: 769 AN: 1455400 Hom.: 0 Cov.: 30 AF XY: 0.000510 AC XY: 369 AN XY: 723592

Gnomad4 AFR exome AF: 0.0000899

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000301

Gnomad4 NFE exome AF: 0.000648

Gnomad4 OTH exome AF: 0.000515

GnomAD4 genome AF: 0.000375 AC: 57 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74344

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.000955

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

NDUFC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	2.3
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs538481040; hg19: chr11-77780922;