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.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Conflicting interpretations of pathogenicity
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)
- Review status:
- criteria provided, conflicting interpretations
- Submissions:
- 3
- First in ClinVar:
- Jan 16, 2017
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Nov 1, 2022
- Accession:
- VCV000374076.4
- Variation ID:
- 374076
- Description:
- single nucleotide variant
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NM_004525.3(LRP2):c.13753C>T (p.Arg4585Ter)
- Allele ID
- 360826
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 2q31.1
- Genomic location
- 2: 169129060 (GRCh38) GRCh38 UCSC
- 2: 169985570 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004525.3:c.13753C>T MANE Select NP_004516.2:p.Arg4585Ter nonsense NC_000002.12:g.169129060G>A NC_000002.11:g.169985570G>A NG_012634.1:g.238553C>T LRG_1300:g.238553C>T LRG_1300t1:c.13753C>T LRG_1300p1:p.Arg4585Ter - Protein change
- R4585*
- Other names
- -
- Canonical SPDI
- NC_000002.12:169129059:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- Trans-Omics for Precision Medicine (TOPMed) 0.00002
- The Genome Aggregation Database (gnomAD) 0.00003
- The Genome Aggregation Database (gnomAD), exomes 0.00001
- Exome Aggregation Consortium (ExAC) 0.00002
- Links
- ClinGen: CA1952430
- dbSNP: rs202057289
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Likely pathogenic | 1 | criteria provided, single submitter | Aug 5, 2015 | RCV000415435.2 | |
| Pathogenic | 1 | criteria provided, single submitter | Nov 1, 2022 | RCV001861449.2 | |
| Uncertain significance | 1 | criteria provided, single submitter | Jan 19, 2022 | RCV002524667.1 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Likely pathogenic
(Aug 05, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492812.1
First in ClinVar: Jan 16, 2017 Last updated: Jan 16, 2017 |
|
|
|
Pathogenic
(Nov 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002228845.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
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 … (more)
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. (less)
|
|
|
Uncertain significance
(Jan 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003595437.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
Not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Number of individuals with the variant: 1
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Variable expression pattern in Donnai-Barrow syndrome: Report of two novel LRP2 mutations and review of the literature. | Khalifa O | European journal of medical genetics | 2015 | PMID: 25682901 |
| Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes. | Kantarci S | Nature genetics | 2007 | PMID: 17632512 |
Text-mined citations for rs202057289...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Feb 07, 2023