rs2239602
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_004525.3(LRP2):c.11498-154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,276 control chromosomes in the GnomAD database, including 62,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.91 ( 62638 hom., cov: 32)
Consequence
LRP2
NM_004525.3 intron
NM_004525.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.107
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
?
Variant 2-169168830-C-T is Benign according to our data. Variant chr2-169168830-C-T is described in ClinVar as [Benign]. Clinvar id is 1245516.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.11498-154G>A | intron_variant | ENST00000649046.1 | |||
LRP2 | XM_011511183.4 | c.11369-154G>A | intron_variant | ||||
LRP2 | XM_011511184.3 | c.9209-154G>A | intron_variant | ||||
LRP2 | XM_047444340.1 | c.10574-154G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.11498-154G>A | intron_variant | NM_004525.3 | P1 | ||||
LRP2 | ENST00000649153.1 | c.2398-154G>A | intron_variant, NMD_transcript_variant | ||||||
LRP2 | ENST00000650252.1 | c.530-154G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.906 AC: 137834AN: 152158Hom.: 62582 Cov.: 32
GnomAD3 genomes
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.906 AC: 137949AN: 152276Hom.: 62638 Cov.: 32 AF XY: 0.903 AC XY: 67273AN XY: 74470
GnomAD4 genome
?
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67273
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74470
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2987
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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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