2-21043879-CCAGCAGCAG-CCAG

Variant names:

• chr2-21043879-CCAGCAG-C
• NM_000384.3:c.61_66delCTGCTG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM4 BP6

The NM_000384.3(APOB):​c.61_66delCTGCTG​(p.Leu21_Leu22del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000632 in 1,265,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: APOB NM_000384.3 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

Genes affected

APOB (HGNC:603): (apolipoprotein B) This gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000384.3.
• BP6: Variant 2-21043879-CCAGCAG-C is Benign according to our data. Variant chr2-21043879-CCAGCAG-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOB	NM_000384.3	c.61_66delCTGCTG	p.Leu21_Leu22del	conservative_inframe_deletion	Exon 1 of 29	ENST00000233242.5	NP_000375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOB	ENST00000233242.5	c.61_66delCTGCTG	p.Leu21_Leu22del	conservative_inframe_deletion	Exon 1 of 29	1	NM_000384.3	ENSP00000233242.1
APOB	ENST00000399256.4	c.61_66delCTGCTG	p.Leu21_Leu22del	conservative_inframe_deletion	Exon 1 of 17	1		ENSP00000382200.4
APOB	ENST00000673739.2	n.61_66delCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 25			ENSP00000501110.2
APOB	ENST00000673882.2	n.61_66delCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 23			ENSP00000501253.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000632 AC: 8 AN: 1265702 Hom.: 0 AF XY: 0.00000320 AC XY: 2 AN XY: 624914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000447

Gnomad4 EAS exome AF: 0.0000330

Gnomad4 SAS exome AF: 0.0000139

Gnomad4 FIN exome AF: 0.0000319

Gnomad4 NFE exome AF: 0.00000401

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr2-21266751;