11-74493326-CAG-TCT

Variant names:

• chr11-74493326-CAG-TCT
• NM_001144869.3:c.376_378delCTGinsAGA
• LIPT2 p.Leu126Arg

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PS1_Moderate

The NM_001144869.3(LIPT2):​c.376_378delCTGinsAGA​(p.Leu126Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LIPT2 NM_001144869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

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]

LIPT2-AS1 (HGNC:56172): (LIPT2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PS1: Transcript NM_001144869.3 (LIPT2) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144869.3. 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
	LIPT2	NM_001144869.3	MANE Select	c.376_378delCTGinsAGA	p.Leu126Arg	missense	N/A	NP_001138341.1	A6NK58
	LIPT2	NM_001329941.2		c.376_378delCTGinsAGA	p.Leu126Arg	missense	N/A	NP_001316870.1
	LIPT2	NM_001329942.2		c.237+139_237+141delCTGinsAGA		intron	N/A	NP_001316871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPT2	ENST00000310109.5	TSL:2 MANE Select	c.376_378delCTGinsAGA	p.Leu126Arg	missense	N/A	ENSP00000309463.4	A6NK58
	LIPT2	ENST00000528085.1	TSL:3	c.180+139_180+141delCTGinsAGA		intron	N/A	ENSP00000433005.1	H0YD50
	LIPT2-AS1	ENST00000526036.1	TSL:1	n.-40_-38delCAGinsTCT		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-74204371;