14-74881980-TC-CT

Variant names:

• chr14-74881980-TC-CT
• NM_001933.5:c.27_28delTCinsCT

Variant summary

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

The NM_001933.5(DLST):​c.27_28delTCinsCT​(p.Arg10Trp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DLST NM_001933.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

DLST (HGNC:2911): (dihydrolipoamide S-succinyltransferase) This gene encodes a mitochondrial protein that belongs to the 2-oxoacid dehydrogenase family. This protein is one of the three components (the E2 component) of the 2-oxoglutarate dehydrogenase complex that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]

DLST Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pheochromocytoma/paraganglioma syndrome 7

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• pyruvate dehydrogenase E1-alpha deficiency

  Inheritance: AR Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001933.5. 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
	DLST	NM_001933.5	MANE Select	c.27_28delTCinsCT	p.Arg10Trp	missense	N/A	NP_001924.2
	DLST	NM_001244883.2		c.27_28delTCinsCT	p.Arg10Trp	missense	N/A	NP_001231812.1	B7Z6J1
	DLST	NR_033814.2		n.65_66delTCinsCT		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLST	ENST00000334220.9	TSL:1 MANE Select	c.27_28delTCinsCT	p.Arg10Trp	missense	N/A	ENSP00000335304.4	P36957-1
	DLST	ENST00000554806.5	TSL:1	c.25_26delTCinsCT	p.Ser9Leu	missense	N/A	ENSP00000451957.1	Q86SW4
	DLST	ENST00000555089.5	TSL:1	n.27_28delTCinsCT		non_coding_transcript_exon	Exon 1 of 12	ENSP00000452422.1	G3V5M3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

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

Other links and lift over

hg19: chr14-75348683;