ClinVar Genomic variation as it relates to human health
NM_014625.4(NPHS2):c.156del (p.Thr53fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_014625.4(NPHS2):c.156del (p.Thr53fs)
Variation ID: 495108 Accession: VCV000495108.10
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 1q25.2 1: 179575709 (GRCh38) [ NCBI UCSC ] 1: 179544844 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 4, 2018 Feb 14, 2024 Jul 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_014625.4:c.156del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055440.1:p.Thr53fs frameshift NM_001297575.2:c.156del NP_001284504.1:p.Thr53fs frameshift NC_000001.11:g.179575712del NC_000001.10:g.179544847del NG_007535.1:g.5241del LRG_887:g.5241del LRG_887t1:c.156del LRG_887p1:p.Thr53fs - Protein change
- T53fs
- Other names
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- Canonical SPDI
- NC_000001.11:179575708:CCCC:CCC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- RNA degradation by nonsense-mediated decay Variation Ontology [VariO:0347]
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NPHS2 | - | - |
GRCh38 GRCh37 |
336 | 545 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV000585728.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 24, 2023 | RCV001853960.5 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Mar 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 2
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Tehran Medical Genetics Laboratory
Accession: SCV000692565.1
First in ClinVar: Mar 04, 2018 Last updated: Mar 04, 2018 |
Clinical Features:
Proteinuria (present)
Age: 0-9 years
Sex: male
Ethnicity/Population group: Iranian
Geographic origin: Middle East
Method: Approximately 37 Mb (214,405 exons) of the Consensus Coding Sequences (CCS) were enriched from fragmented genomic DNA by >340,000 probes designed against the human genome (Nextera Rapid Capture Exome, Illumina) and the generated library sequenced on an Illumina platform to an average coverage depth 70-100X. An end to end inhouse bioinformatics pipelines including base calling, primary filtering of low quality reads and probable artifacts, and annotation of variants was applied.
Testing laboratory: Centogene
Date variant was reported to submitter: 2017-03-27
Testing laboratory interpretation: Likely pathogenic
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Likely pathogenic
(Oct 24, 2017)
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criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000795001.1
First in ClinVar: Mar 04, 2018 Last updated: Mar 04, 2018 |
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Pathogenic
(Jun 07, 2019)
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criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 2
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001150186.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: male
Tissue: blood
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Likely pathogenic
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Nephrotic syndrome, type 2
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004049298.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002247045.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 495108). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 495108). This premature translational stop signal has been observed in individual(s) with nephrotic syndrome (PMID: 28117080). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr53Profs*46) in the NPHS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHS2 are known to be pathogenic (PMID: 10742096, 14701729, 15253708, 23595123). (less)
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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RNA degradation by nonsense-mediated decay
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Tehran Medical Genetics Laboratory
Accession: SCV000692565.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. | Bierzynska A | Kidney international | 2017 | PMID: 28117080 |
A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families. | Al-Hamed MH | Journal of human genetics | 2013 | PMID: 23595123 |
NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. | Weber S | Kidney international | 2004 | PMID: 15253708 |
Early glomerular filtration defect and severe renal disease in podocin-deficient mice. | Roselli S | Molecular and cellular biology | 2004 | PMID: 14701729 |
NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. | Boute N | Nature genetics | 2000 | PMID: 10742096 |
Text-mined citations for rs1272948499 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.