rs149469954
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_004525.3(LRP2):c.5209C>T(p.Leu1737Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,613,992 control chromosomes in the GnomAD database, including 3 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
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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.5209C>T | p.Leu1737Phe | missense_variant | 31/79 | ENST00000649046.1 | |
LRP2 | XM_011511183.4 | c.5209C>T | p.Leu1737Phe | missense_variant | 31/78 | ||
LRP2 | XM_047444340.1 | c.4285C>T | p.Leu1429Phe | missense_variant | 31/79 | ||
LRP2 | XM_011511184.3 | c.2920C>T | p.Leu974Phe | missense_variant | 16/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.5209C>T | p.Leu1737Phe | missense_variant | 31/79 | NM_004525.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00126 AC: 191AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00120 AC: 300AN: 250994Hom.: 2 AF XY: 0.00120 AC XY: 163AN XY: 135634
GnomAD4 exome AF: 0.00154 AC: 2256AN: 1461750Hom.: 3 Cov.: 31 AF XY: 0.00149 AC XY: 1083AN XY: 727200
GnomAD4 genome ? AF: 0.00125 AC: 191AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.00113 AC XY: 84AN XY: 74440
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | LRP2: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2020 | This variant is associated with the following publications: (PMID: 25533962) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Donnai-Barrow syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | May 22, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 12, 2014 | - - |
LRP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 12, 2019 | This variant is classified as 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