14-74889365-C-CT

Position:

• chr14-74889365-C-CT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001933.5(DLST):​c.274+17dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 123,770 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLST NM_001933.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.357

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-74889365-C-CT is Benign according to our data. Variant chr14-74889365-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 2814804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 539 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLST	NM_001933.5	c.274+17dup		intron_variant		ENST00000334220.9	NP_001924.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLST	ENST00000334220.9	c.274+17dup		intron_variant		1	NM_001933.5	ENSP00000335304	P1

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 539 AN: 123754 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00180

Gnomad ASJ AF: 0.00196

Gnomad EAS AF: 0.000226

Gnomad SAS AF: 0.00252

Gnomad FIN AF: 0.00118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00635

Gnomad OTH AF: 0.00413

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00152 AC: 1973 AN: 1300276 Hom.: 0 Cov.: 29 AF XY: 0.00141 AC XY: 915 AN XY: 650588

Gnomad4 AFR exome AF: 0.000483

Gnomad4 AMR exome AF: 0.000292

Gnomad4 ASJ exome AF: 0.000334

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000537

Gnomad4 FIN exome AF: 0.0000984

Gnomad4 NFE exome AF: 0.00185

Gnomad4 OTH exome AF: 0.000906

GnomAD4 genome AF: 0.00435 AC: 539 AN: 123770 Hom.: 1 Cov.: 31 AF XY: 0.00438 AC XY: 258 AN XY: 58934

Gnomad4 AFR AF: 0.00328

Gnomad4 AMR AF: 0.00180

Gnomad4 ASJ AF: 0.00196

Gnomad4 EAS AF: 0.000227

Gnomad4 SAS AF: 0.00252

Gnomad4 FIN AF: 0.00118

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.00411

Alfa AF: 0.00133 Hom.: 0

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs774104075; hg19: chr14-75356068;