2-169127290-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004525.3(LRP2):c.*1373A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Consequence
LRP2
NM_004525.3 3_prime_UTR
NM_004525.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.717
Genes affected
LRP2 (HGNC:6694): (LDL receptor related protein 2) The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LRP2 | NM_004525.3 | c.*1373A>T | 3_prime_UTR_variant | 79/79 | ENST00000649046.1 | NP_004516.2 | ||
| LRP2 | XM_011511183.4 | c.*1373A>T | 3_prime_UTR_variant | 78/78 | XP_011509485.1 | |||
| LRP2 | XM_047444340.1 | c.*1373A>T | 3_prime_UTR_variant | 79/79 | XP_047300296.1 | |||
| LRP2 | XM_011511184.3 | c.*1373A>T | 3_prime_UTR_variant | 64/64 | XP_011509486.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 31
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GnomAD4 genome 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Donnai-Barrow syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at