rs147058423
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_004525.3(LRP2):c.3110G>A(p.Arg1037Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,614,196 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004525.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.3110G>A | p.Arg1037Lys | missense_variant | 21/79 | ENST00000649046.1 | |
LRP2 | XM_011511183.4 | c.3110G>A | p.Arg1037Lys | missense_variant | 21/78 | ||
LRP2 | XM_047444340.1 | c.2186G>A | p.Arg729Lys | missense_variant | 21/79 | ||
LRP2 | XM_011511184.3 | c.821G>A | p.Arg274Lys | missense_variant | 6/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.3110G>A | p.Arg1037Lys | missense_variant | 21/79 | NM_004525.3 | P1 | ||
LRP2 | ENST00000443831.1 | c.2699G>A | p.Arg900Lys | missense_variant | 19/23 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00124 AC: 188AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00127 AC: 319AN: 251480Hom.: 0 AF XY: 0.00129 AC XY: 176AN XY: 135910
GnomAD4 exome AF: 0.00196 AC: 2868AN: 1461884Hom.: 2 Cov.: 31 AF XY: 0.00196 AC XY: 1423AN XY: 727242
GnomAD4 genome ? AF: 0.00123 AC: 188AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000967 AC XY: 72AN XY: 74488
ClinVar
Submissions by phenotype
Donnai-Barrow syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 17, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 17, 2014 | - - |
LRP2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 26, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at