rs202057289
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_004525.3(LRP2):c.13753C>T(p.Arg4585Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,610,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004525.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.13753C>T | p.Arg4585Ter | stop_gained | 78/79 | ENST00000649046.1 | NP_004516.2 | |
LRP2 | XM_011511183.4 | c.13624C>T | p.Arg4542Ter | stop_gained | 77/78 | XP_011509485.1 | ||
LRP2 | XM_047444340.1 | c.12829C>T | p.Arg4277Ter | stop_gained | 78/79 | XP_047300296.1 | ||
LRP2 | XM_011511184.3 | c.11464C>T | p.Arg3822Ter | stop_gained | 63/64 | XP_011509486.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.13753C>T | p.Arg4585Ter | stop_gained | 78/79 | NM_004525.3 | ENSP00000496870 | P1 | ||
LRP2 | ENST00000649153.1 | c.*477C>T | 3_prime_UTR_variant, NMD_transcript_variant | 29/30 | ENSP00000497617 | |||||
LRP2 | ENST00000650252.1 | c.*1427C>T | 3_prime_UTR_variant, NMD_transcript_variant | 23/24 | ENSP00000496887 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251182Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135748
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1458884Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 13AN XY: 725958
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74286
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 06, 2023 | This sequence change creates a premature translational stop signal (p.Arg4585*) in the LRP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LRP2 are known to be pathogenic (PMID: 17632512, 25682901). This variant is present in population databases (rs202057289, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 374076). For these reasons, this variant has been classified as Pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 2023 | Nonsense variant predicted to result in protein truncation, as the last 71 amino acids are lost; Has not been previously published as pathogenic or benign to our knowledge - |
Prolactin-producing pituitary gland adenoma;C0271183:High myopia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Aug 05, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2022 | Not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at