chr11-74492212-C-A

Variant names:

• chr11-74492212-C-A
• NM_001144869.3:c.619G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144869.3(LIPT2):​c.619G>T​(p.Glu207*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000715 in 1,399,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LIPT2 NM_001144869.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81

Genes affected

LIPT2 (HGNC:37216): (lipoyl(octanoyl) transferase 2) This gene encodes a mitochondrial protein that catalyzes the transfer of octanoic acid to lipoate-dependent enzymes such as octanoyl-ACP. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3	c.619G>T	p.Glu207*	stop_gained	Exon 2 of 2	ENST00000310109.5	NP_001138341.1
LIPT2	NM_001329941.2	c.*33G>T		3_prime_UTR_variant	Exon 2 of 2		NP_001316870.1
LIPT2	NM_001329942.2	c.*33G>T		3_prime_UTR_variant	Exon 2 of 2		NP_001316871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPT2	ENST00000310109.5	c.619G>T	p.Glu207*	stop_gained	Exon 2 of 2	2	NM_001144869.3	ENSP00000309463.4
LIPT2	ENST00000527115	c.*33G>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000431210.1
LIPT2	ENST00000528085.1	c.*116G>T		downstream_gene_variant		3		ENSP00000433005.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399434 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Uncertain	0.96	D
Vest4		0.26
GERP RS		5.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-74203257;