NM_000527.5:c.2552delA
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_000527.5(LDLR):c.2552delA(p.Gln851ArgfsTer78) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
LDLR
NM_000527.5 frameshift
NM_000527.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.67
Publications
0 publications found
Genes affected
LDLR (HGNC:6547): (low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.012 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-11131284-CA-C is Pathogenic according to our data. Variant chr19-11131284-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 252359.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000527.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| LDLR | MANE Select | c.2552delA | p.Gln851ArgfsTer78 | frameshift | Exon 18 of 18 | NP_000518.1 | P01130-1 | ||
| LDLR | c.2429delA | p.Gln810ArgfsTer78 | frameshift | Exon 17 of 17 | NP_001182728.1 | P01130-4 | |||
| LDLR | c.2048delA | p.Gln683ArgfsTer78 | frameshift | Exon 16 of 16 | NP_001182729.1 | P01130-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LDLR | TSL:1 MANE Select | c.2552delA | p.Gln851ArgfsTer78 | frameshift | Exon 18 of 18 | ENSP00000454071.1 | P01130-1 | ||
| LDLR | TSL:1 | c.2810delA | p.Gln937ArgfsTer78 | frameshift | Exon 18 of 18 | ENSP00000252444.6 | J3KMZ9 | ||
| LDLR | TSL:1 | c.2548-2delA | splice_acceptor intron | N/A | ENSP00000453346.1 | P01130-5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Hypercholesterolemia, familial, 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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