2-210203382-CCTGGT-AAACATAACATTCATG

Position:

• chr2-210203382-CCTGGT-AAACATAACATTCATG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The ENST00000233710.4(ACADL):​c.928_933delinsCATGAATGTTATGTTT​(p.Thr310HisfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACADL ENST00000233710.4 frameshift
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 7.48

Genes affected

ACADL (HGNC:88): (acyl-CoA dehydrogenase long chain) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-210203382-CCTGGT-AAACATAACATTCATG is Benign according to our data. Variant chr2-210203382-CCTGGT-AAACATAACATTCATG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 632339.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADL	NM_001608.4	c.928_933delinsCATGAATGTTATGTTT	p.Thr310HisfsTer6	frameshift_variant	8/11	ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5	c.865_870delinsCATGAATGTTATGTTT	p.Thr289HisfsTer6	frameshift_variant	8/11		XP_005246574.1
ACADL	XM_047444103.1	c.505_510delinsCATGAATGTTATGTTT	p.Thr169HisfsTer6	frameshift_variant	8/11		XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADL	ENST00000233710.4	c.928_933delinsCATGAATGTTATGTTT	p.Thr310HisfsTer6	frameshift_variant	8/11	1	NM_001608.4	ENSP00000233710	P1
	ENST00000639259.2	n.280-26901_280-26896delinsAAACATAACATTCATG		intron_variant, non_coding_transcript_variant		5
ACADL	ENST00000652584.1	n.1156_1161delinsCATGAATGTTATGTTT		non_coding_transcript_exon_variant	8/11
	ENST00000412065.1	n.313-15090_313-15085delinsAAACATAACATTCATG		intron_variant, non_coding_transcript_variant		4

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

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Very long chain acyl-CoA dehydrogenase deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 16, 2018

The ACADL c.928_933delACCAGGinsCATGAATGTTATGTTT (p.Thr310HisfsTer6) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance, but suspicious for pathogenicity for long-chain acyl-CoA dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1559636157; hg19: chr2-211068106;