Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate this variant leads to loss of splice acceptor resulting in skipping of exon 20 (Molinari et al., 2018); This variant is associated with the following publications: (PMID: 27894351, 28973083, 30002499, 34426522, 32055034, 31980526, 32552793, 32901917, 20007846, 18371931, 33726816, 27535533)
ClinVar Genomic variation as it relates to human health
NM_153240.5(NPHP3):c.2694-2_2694-1del
Germline
Classification
Help
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.
(24)
Help
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.
Pathogenic/Likely pathogenic
24
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_153240.5(NPHP3):c.2694-2_2694-1del
Variation ID: 220868 Accession: VCV000220868.54
- Type and length
-
Deletion, 2 bp
- Location
-
Cytogenetic: 3q22.1 3: 132689264-132689265 (GRCh38) [ NCBI UCSC ] 3: 132408108-132408109 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 22, 2016 Nov 24, 2024 Mar 29, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_153240.5:c.2694-2_2694-1del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_153240.4:c.2694-2_2694-1del NC_000003.12:g.132689264_132689265del NC_000003.11:g.132408108_132408109del NG_008130.2:g.38168_38169del - Protein change
- -
- Other names
-
splice site
- Canonical SPDI
- NC_000003.12:132689263:CT:
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00024
The Genome Aggregation Database (gnomAD) 0.00026
Trans-Omics for Precision Medicine (TOPMed) 0.00026
The Genome Aggregation Database (gnomAD), exomes 0.00027
Exome Aggregation Consortium (ExAC) 0.00036
1000 Genomes Project 30x 0.00047
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
| NPHP3 | - | - |
GRCh38 GRCh37 |
6 | 1207 | |
| NPHP3-ACAD11 | - | - | - | GRCh38 | - | 1474 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Aug 12, 2019 | RCV000002753.16 | |
| Pathogenic (2) |
criteria provided, single submitter
|
May 2, 2023 | RCV000055628.11 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 26, 2024 | RCV000205615.14 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV000256425.7 | |
| Pathogenic/Likely pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Jun 1, 2022 | RCV000355185.32 | |
| Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Mar 29, 2024 | RCV000593585.13 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 21, 2021 | RCV002500658.3 | |
|
NPHP3-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Aug 27, 2024 | RCV004530240.2 |
Submissions - Germline
| Classification
Help
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
Help
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
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 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
(Sep 16, 2018)
|
criteria provided, single submitter
Method: research
|
not provided
Affected status: yes
Allele origin:
germline
|
Gharavi Laboratory, Columbia University
Accession: SCV000809211.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
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Pathogenic
(Mar 15, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000706826.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 3
Sex: mixed
|
|
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Pathogenic
(May 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000329431.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate this variant leads to loss … (more)
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate this variant leads to loss of splice acceptor resulting in skipping of exon 20 (Molinari et al., 2018); This variant is associated with the following publications: (PMID: 27894351, 28973083, 30002499, 34426522, 32055034, 31980526, 32552793, 32901917, 20007846, 18371931, 33726816, 27535533) (less)
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Pathogenic
(May 02, 2023)
|
criteria provided, single submitter
Method: curation
|
Renal-hepatic-pancreatic dysplasia 1
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Study: Broad Institute Center for Mendelian Genomics (CMG)
Accession: SCV000693903.2 First in ClinVar: Jan 23, 2018 Last updated: May 06, 2023 |
Comment:
The heterozygous c.2694-2_2694-1del variant in NPHP3 was identified by our study in one individual with renal-hepatic-pancreatic dysplasia 1. Trio exome analysis showed this variant to … (more)
The heterozygous c.2694-2_2694-1del variant in NPHP3 was identified by our study in one individual with renal-hepatic-pancreatic dysplasia 1. Trio exome analysis showed this variant to be in trans with a likely pathogenic variant (ClinVar Variation ID: 635041). The c.2694-2_2694-1del variant in NPHP3 has been previously reported in 22 unrelated individuals with NPHP3-related disease (PMID: 33532864, PMID: 28973083, PMID: 32055034, PMID: 32552793, PMID: 32901917, PMID: 27894351, PMID: 33726816, PMID: 23559409, PMID: 26673778, PMID: 30002499, PMID: 33323469), but has been identified in 0.04% (14/30612) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs963574014). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. Of these 22 previously reported unrelated individuals (PMID: 33532864, PMID: 28973083, PMID: 32055034, PMID: 32552793, PMID: 32901917, PMID: 27894351, PMID: 33726816, PMID: 23559409, PMID: 26673778, PMID: 30002499, PMID: 33323469), 12 were homozygotes (PMID: 32055034, PMID: 32552793, PMID: 27894351, PMID: 18371931, PMID: 20007846) and 4 were compound heterozygotes who carried pathogenic or likely pathogenic variants in trans (PMID: 33532864, ClinVar Variation ID: 659899; PMID: 28973083, ClinVar Variation ID: 988261; PMID: 23559409, ClinVar Variation ID: 96511, ClinVar Variation ID: 693989 ; PMID: 30002499, ClinVar Variation ID: 262696; PMID: 33323469, ClinVar Variation ID: 1454640), which increases the likelihood that the c.2694-2_2694-1del variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 220868) and has been interpreted as pathogenic by multiple submitters. RT-PCR analysis performed on affected tissue shows evidence of altered splicing of exon 20 (PMID: 32552793, PMID: 30002499, PMID: 20007846). A different nucleotide change that also results in a splice acceptor variant at the same site, c.2694-2A>T (ClinVar Variation ID: 1524627), has been previously reported likely pathogenic, and the variant being assessed here, c.2694-2_2694-1del, is predicted by SpliceAI to have a similar effect on splicing. This variant is located in the 3' splice region. Computational tools do suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. There is an in-frame cryptic splice site 21 bases from the intron-exon boundary, providing evidence that this variant may delete 7 amino acids instead of causing loss of function. However, this information is not predictive enough to determine pathogenicity. Loss of function of the NPHP3 gene is an established disease mechanism in autosomal recessive renal-hepatic-pancreatic dysplasia 1. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive renal-hepatic-pancreatic dysplasia 1. ACMG/AMP Criteria applied: PVS1_Moderate, PS1_Supporting, PS3_Moderate, PM3_VeryStrong (Richards 2015). (less)
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Pathogenic
(Jan 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Nephronophthisis
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000261757.11
First in ClinVar: Feb 02, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects a splice site in intron 19 of the NPHP3 gene. RNA analysis indicates that disruption of this splice site induces altered … (more)
This sequence change affects a splice site in intron 19 of the NPHP3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs751527253, gnomAD 0.05%). Disruption of this splice site has been observed in individual(s) with Meckel-Gruber-like syndrome and/or nephronophthisis-related ciliopathy (PMID: 18371931, 20007846, 23559409, 26673778). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 220868). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 20007846). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 01, 2020)
|
criteria provided, single submitter
Method: research
|
Nephronophthisis 3
Affected status: yes
Allele origin:
germline
|
Molecular Biology Laboratory, Fundació Puigvert
Study: KidneyPanel_2020
Accession: SCV001425113.1 First in ClinVar: Jan 17, 2021 Last updated: Jan 17, 2021 |
|
|
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Pathogenic
(Aug 12, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
NPHP3-related Meckel-like syndrome
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369566.2
First in ClinVar: Jul 06, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PS3,PM2.
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|
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Pathogenic
(Oct 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Nephronophthisis 3
Affected status: yes
Allele origin:
unknown
|
3billion
Accession: SCV002012327.1
First in ClinVar: Nov 11, 2021 Last updated: Nov 11, 2021 |
Comment:
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. … (more)
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0002759, PM2).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000220868.16). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Renal tubular atrophy (present) , Focal segmental glomerulosclerosis (present) , Abnormal renal morphology (present) , Growth delay (present) , Specific learning disability (present) , Stage … (more)
Renal tubular atrophy (present) , Focal segmental glomerulosclerosis (present) , Abnormal renal morphology (present) , Growth delay (present) , Specific learning disability (present) , Stage 5 chronic kidney disease (present) , Short stature (present) , Intellectual disability (present) (less)
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Pathogenic
(May 24, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501393.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
|
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Pathogenic
(Dec 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Renal-hepatic-pancreatic dysplasia 1
NPHP3-related Meckel-like syndrome Nephronophthisis 3
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002810601.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NPHP3-related Meckel-like syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047650.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The splice site c.2694-2_2694-1del variant has been reported to segregate with Meckel syndrome and embryonic lethality in families (Bergmann et. al., 2008). An experimental study … (more)
The splice site c.2694-2_2694-1del variant has been reported to segregate with Meckel syndrome and embryonic lethality in families (Bergmann et. al., 2008). An experimental study has shown that this variant results in altered splicing, likely by usage of a cryptic splice site, resulting in a prematurely truncated protein (Fiskerstrand et. al., 2010). The c.2694-2_2694-1del variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.02759% in gnomAD database. This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (Baralle D, Baralle M., 2005), and loss-of-function variants in NPHP3 are known to be pathogenic (Halbritter et. al., 2013). For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed. The same variant (c.2694-2_2694-1del) has been observed in her father. (less)
Clinical Features:
Neurodevelopmental delay (present) , Motor stereotypies (present) , Strabismus (present) , Abnormal visual fixation (present) , Spasticity (present) , Hyperreflexia (present) , Ankle flexion contracture … (more)
Neurodevelopmental delay (present) , Motor stereotypies (present) , Strabismus (present) , Abnormal visual fixation (present) , Spasticity (present) , Hyperreflexia (present) , Ankle flexion contracture (present) , Optic neuropathy (present) , Cerebral atrophy (present) , Dandy-Walker malformation (present) (less)
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Likely pathogenic
(Dec 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Nephronophthisis 3
Affected status: yes
Allele origin:
maternal
|
Precision Medicine Center, Zhengzhou University
Accession: SCV004218469.1
First in ClinVar: Jun 23, 2024 Last updated: Jun 23, 2024 |
Comment:
PVS1,PM2_p
Sex: female
|
|
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Pathogenic
(Mar 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Nephronophthisis 3
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004807901.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
|
|
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Pathogenic
(Jun 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002544835.16
First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024 |
Comment:
NPHP3: PVS1, PS3:Supporting, PS4:Supporting
Number of individuals with the variant: 1
|
|
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Pathogenic
(Mar 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Nephronophthisis 3
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002766885.2
First in ClinVar: Dec 24, 2022 Last updated: Nov 24, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Meckel syndrome 7 (MIM# 267010), nephronophthisis 3 (MIM# 604387) and renal-hepatic-pancreatic dysplasia 1 (MIM# 208540). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0210 - Splice site variant proven to affect splicing of the transcript with a known effect on protein sequence. RT-PCR done on whole blood RNA of an affected individual demonstrated exon 20 skipping, which is expected to result in a frameshift (PMID: 30002499). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 78 heterozygotes, 0 homozygotes). (SP) 0311 - An alternative nucleotide change at the same canonical splice site is present in gnomAD (v3: 1 heterozygote, 0 homozygotes). (SB) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten individuals described to have nephronophthisis, end stage renal disease or ciliopathy syndrome and consistently classified as pathogenic by diagnostic laboratories in ClinVar (PMID: 28921755, 30002499, 32055034). (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Polycystic kidney disease
Affected status: yes
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV000322802.1
First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016 |
Clinical Features:
Lethal polycystic kidney disease with positive family history (present) , Lethal polycystic kidney disease (present)
|
|
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Pathogenic
(Jan 01, 2010)
|
no assertion criteria provided
Method: literature only
|
MECKEL SYNDROME, TYPE 7
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022911.6
First in ClinVar: Apr 04, 2013 Last updated: Dec 15, 2018 |
Comment on evidence:
Meckel Syndrome, Type 7 Bergmann et al. (2008) reported 2 female fetuses (family 806), born of consanguineous Turkish parents, with enlarged renal-hepatic-pancreatic dysplasia; one of … (more)
Meckel Syndrome, Type 7 Bergmann et al. (2008) reported 2 female fetuses (family 806), born of consanguineous Turkish parents, with enlarged renal-hepatic-pancreatic dysplasia; one of the fetuses also had Dandy-Walker cyst. The features were consistent with Meckel syndrome-7 (MKS7; 267010). In both fetuses, Bergmann et al. (2008) identified a homozygous deletion in the intron 19 splice acceptor site of the NPHP3 gene (c.2694-1_2 del), resulting in premature protein truncation. One pregnancy was terminated at 23 weeks, and one fetus died in the perinatal period. Both had multicystic dysplastic kidneys and hepatic ductal plate malformation. One had aortic stenosis. Renal-Hepatic-Pancreatic Dysplasia 1 Fiskerstrand et al. (2010) reported 2 Norwegian sibs, born to remotely consanguineous parents, with lethal renal-hepatic-pancreatic dysplasia-1 (RHPD1; 208540) who were homozygous for an AG deletion in intron 19 of the NPHP3 gene. The first child had intrauterine growth retardation, Potter facies with hypertelorism, beak-like nose, short neck, and short sternum, and died of respiratory insufficiency 1 day after birth. The pregnancy was complicated by oligohydramnios. The lungs and kidneys were hypoplastic, and the kidneys contained multiple small cysts and were dysplastic. The pancreas was enlarged, fibrotic, and showed irregular ducts and atrophy of acini. There was portal fibrosis and paucity of bile ducts in the liver. The brain was normal. The second pregnancy resulted in elective termination at 16 weeks because of multiple abnormalities in the fetus. The fetus had dysmorphic features consistent with Potter facies and flexion contractures of multiple joints. There was complete situs inversus of the thoracic and abdominal organs. Microscopic studies showed renal dysplasia, hepatic ductal plate malformation, and dysplasia of the pancreas with dilated ductal structures with scarce lobular differentiation. Although the brain was grossly normal, there was evidence of polymicrogyria. Fiskerstrand et al. (2010) noted the phenotypic similarities to the Turkish patients reported by Bergmann et al. (2008). (less)
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Pathogenic
(Jan 01, 2010)
|
no assertion criteria provided
Method: literature only
|
RENAL-HEPATIC-PANCREATIC DYSPLASIA 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000083853.5
First in ClinVar: Sep 20, 2013 Last updated: Dec 15, 2018 |
Comment on evidence:
Meckel Syndrome, Type 7 Bergmann et al. (2008) reported 2 female fetuses (family 806), born of consanguineous Turkish parents, with enlarged renal-hepatic-pancreatic dysplasia; one of … (more)
Meckel Syndrome, Type 7 Bergmann et al. (2008) reported 2 female fetuses (family 806), born of consanguineous Turkish parents, with enlarged renal-hepatic-pancreatic dysplasia; one of the fetuses also had Dandy-Walker cyst. The features were consistent with Meckel syndrome-7 (MKS7; 267010). In both fetuses, Bergmann et al. (2008) identified a homozygous deletion in the intron 19 splice acceptor site of the NPHP3 gene (c.2694-1_2 del), resulting in premature protein truncation. One pregnancy was terminated at 23 weeks, and one fetus died in the perinatal period. Both had multicystic dysplastic kidneys and hepatic ductal plate malformation. One had aortic stenosis. Renal-Hepatic-Pancreatic Dysplasia 1 Fiskerstrand et al. (2010) reported 2 Norwegian sibs, born to remotely consanguineous parents, with lethal renal-hepatic-pancreatic dysplasia-1 (RHPD1; 208540) who were homozygous for an AG deletion in intron 19 of the NPHP3 gene. The first child had intrauterine growth retardation, Potter facies with hypertelorism, beak-like nose, short neck, and short sternum, and died of respiratory insufficiency 1 day after birth. The pregnancy was complicated by oligohydramnios. The lungs and kidneys were hypoplastic, and the kidneys contained multiple small cysts and were dysplastic. The pancreas was enlarged, fibrotic, and showed irregular ducts and atrophy of acini. There was portal fibrosis and paucity of bile ducts in the liver. The brain was normal. The second pregnancy resulted in elective termination at 16 weeks because of multiple abnormalities in the fetus. The fetus had dysmorphic features consistent with Potter facies and flexion contractures of multiple joints. There was complete situs inversus of the thoracic and abdominal organs. Microscopic studies showed renal dysplasia, hepatic ductal plate malformation, and dysplasia of the pancreas with dilated ductal structures with scarce lobular differentiation. Although the brain was grossly normal, there was evidence of polymicrogyria. Fiskerstrand et al. (2010) noted the phenotypic similarities to the Turkish patients reported by Bergmann et al. (2008). (less)
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Pathogenic
(Jun 15, 2018)
|
no assertion criteria provided
Method: research
|
Nephronophthisis 3
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV000924491.1
First in ClinVar: Jun 24, 2019 Last updated: Jun 24, 2019 |
Comment:
The heterozygous c.2694-2_2694-1delAG variant was identified by our study in the compound heterozygous state, with a pathogenic variant, in one individual with nephronophthisis. This variant … (more)
The heterozygous c.2694-2_2694-1delAG variant was identified by our study in the compound heterozygous state, with a pathogenic variant, in one individual with nephronophthisis. This variant is pathogenic based off of multiple reports in ClinVar and the literature. (less)
Clinical Features:
Congenital syndromic ciliopathy (present) , Enlarged-cystic kidneys (present) , Congenital heart desease (present) , Situs inversus (present) , Perinatal death (respiratory distress) (present)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001806968.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742234.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001967526.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037362.1 First in ClinVar: Dec 21, 2021 Last updated: Dec 21, 2021 |
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Pathogenic
(Aug 27, 2024)
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no assertion criteria provided
Method: clinical testing
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NPHP3-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004115080.3
First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024 |
Comment:
The NPHP3 c.2694-2_2694-1delAG variant is predicted to result in a deletion affecting a canonical splice site. This variant has been reported in the homozygous and … (more)
The NPHP3 c.2694-2_2694-1delAG variant is predicted to result in a deletion affecting a canonical splice site. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with NPHP3 related disorders (Bergmann et al. 2008. PubMed ID: 18371931; Meng et al 2017. PubMed ID: 28973083; Shaheen et al 2016. PubMed ID: 27894351; Shamseldin et al. 2021. PubMed ID: 34645488). Expression assays reveal that this variant leads to skipping of exon 20 (Maddirevula et al. 2020. PubMed ID: 32552793). This variant is reported in 0.046% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic. (less)
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Comment:
Comment:
The heterozygous c.2694-2_2694-1del variant in NPHP3 was identified by our study in one individual with renal-hepatic-pancreatic dysplasia 1. Trio exome analysis showed this variant to be in trans with a likely pathogenic variant (ClinVar Variation ID: 635041). The c.2694-2_2694-1del variant in NPHP3 has been previously reported in 22 unrelated individuals with NPHP3-related disease (PMID: 33532864, PMID: 28973083, PMID: 32055034, PMID: 32552793, PMID: 32901917, PMID: 27894351, PMID: 33726816, PMID: 23559409, PMID: 26673778, PMID: 30002499, PMID: 33323469), but has been identified in 0.04% (14/30612) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs963574014). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. Of these 22 previously reported unrelated individuals (PMID: 33532864, PMID: 28973083, PMID: 32055034, PMID: 32552793, PMID: 32901917, PMID: 27894351, PMID: 33726816, PMID: 23559409, PMID: 26673778, PMID: 30002499, PMID: 33323469), 12 were homozygotes (PMID: 32055034, PMID: 32552793, PMID: 27894351, PMID: 18371931, PMID: 20007846) and 4 were compound heterozygotes who carried pathogenic or likely pathogenic variants in trans (PMID: 33532864, ClinVar Variation ID: 659899; PMID: 28973083, ClinVar Variation ID: 988261; PMID: 23559409, ClinVar Variation ID: 96511, ClinVar Variation ID: 693989 ; PMID: 30002499, ClinVar Variation ID: 262696; PMID: 33323469, ClinVar Variation ID: 1454640), which increases the likelihood that the c.2694-2_2694-1del variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 220868) and has been interpreted as pathogenic by multiple submitters. RT-PCR analysis performed on affected tissue shows evidence of altered splicing of exon 20 (PMID: 32552793, PMID: 30002499, PMID: 20007846). A different nucleotide change that also results in a splice acceptor variant at the same site, c.2694-2A>T (ClinVar Variation ID: 1524627), has been previously reported likely pathogenic, and the variant being assessed here, c.2694-2_2694-1del, is predicted by SpliceAI to have a similar effect on splicing. This variant is located in the 3' splice region. Computational tools do suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. There is an in-frame cryptic splice site 21 bases from the intron-exon boundary, providing evidence that this variant may delete 7 amino acids instead of causing loss of function. However, this information is not predictive enough to determine pathogenicity. Loss of function of the NPHP3 gene is an established disease mechanism in autosomal recessive renal-hepatic-pancreatic dysplasia 1. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive renal-hepatic-pancreatic dysplasia 1. ACMG/AMP Criteria applied: PVS1_Moderate, PS1_Supporting, PS3_Moderate, PM3_VeryStrong (Richards 2015).
Comment:
This sequence change affects a splice site in intron 19 of the NPHP3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs751527253, gnomAD 0.05%). Disruption of this splice site has been observed in individual(s) with Meckel-Gruber-like syndrome and/or nephronophthisis-related ciliopathy (PMID: 18371931, 20007846, 23559409, 26673778). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 220868). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 20007846). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PS3,PM2.
Comment:
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0002759, PM2).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000220868.16). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
The splice site c.2694-2_2694-1del variant has been reported to segregate with Meckel syndrome and embryonic lethality in families (Bergmann et. al., 2008). An experimental study has shown that this variant results in altered splicing, likely by usage of a cryptic splice site, resulting in a prematurely truncated protein (Fiskerstrand et. al., 2010). The c.2694-2_2694-1del variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.02759% in gnomAD database. This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (Baralle D, Baralle M., 2005), and loss-of-function variants in NPHP3 are known to be pathogenic (Halbritter et. al., 2013). For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed. The same variant (c.2694-2_2694-1del) has been observed in her father.
Comment:
PVS1,PM2_p
Comment:
NPHP3: PVS1, PS3:Supporting, PS4:Supporting
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Meckel syndrome 7 (MIM# 267010), nephronophthisis 3 (MIM# 604387) and renal-hepatic-pancreatic dysplasia 1 (MIM# 208540). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0210 - Splice site variant proven to affect splicing of the transcript with a known effect on protein sequence. RT-PCR done on whole blood RNA of an affected individual demonstrated exon 20 skipping, which is expected to result in a frameshift (PMID: 30002499). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 78 heterozygotes, 0 homozygotes). (SP) 0311 - An alternative nucleotide change at the same canonical splice site is present in gnomAD (v3: 1 heterozygote, 0 homozygotes). (SB) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten individuals described to have nephronophthisis, end stage renal disease or ciliopathy syndrome and consistently classified as pathogenic by diagnostic laboratories in ClinVar (PMID: 28921755, 30002499, 32055034). (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
The heterozygous c.2694-2_2694-1delAG variant was identified by our study in the compound heterozygous state, with a pathogenic variant, in one individual with nephronophthisis. This variant is pathogenic based off of multiple reports in ClinVar and the literature.
Comment:
The NPHP3 c.2694-2_2694-1delAG variant is predicted to result in a deletion affecting a canonical splice site. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with NPHP3 related disorders (Bergmann et al. 2008. PubMed ID: 18371931; Meng et al 2017. PubMed ID: 28973083; Shaheen et al 2016. PubMed ID: 27894351; Shamseldin et al. 2021. PubMed ID: 34645488). Expression assays reveal that this variant leads to skipping of exon 20 (Maddirevula et al. 2020. PubMed ID: 32552793). This variant is reported in 0.046% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic.
Germline Functional Evidence
| 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. |
Comment:
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate this variant leads to loss of splice acceptor resulting in skipping of exon 20 (Molinari et al., 2018); This variant is associated with the following publications: (PMID: 27894351, 28973083, 30002499, 34426522, 32055034, 31980526, 32552793, 32901917, 20007846, 18371931, 33726816, 27535533)
Comment:
The heterozygous c.2694-2_2694-1del variant in NPHP3 was identified by our study in one individual with renal-hepatic-pancreatic dysplasia 1. Trio exome analysis showed this variant to be in trans with a likely pathogenic variant (ClinVar Variation ID: 635041). The c.2694-2_2694-1del variant in NPHP3 has been previously reported in 22 unrelated individuals with NPHP3-related disease (PMID: 33532864, PMID: 28973083, PMID: 32055034, PMID: 32552793, PMID: 32901917, PMID: 27894351, PMID: 33726816, PMID: 23559409, PMID: 26673778, PMID: 30002499, PMID: 33323469), but has been identified in 0.04% (14/30612) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs963574014). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. Of these 22 previously reported unrelated individuals (PMID: 33532864, PMID: 28973083, PMID: 32055034, PMID: 32552793, PMID: 32901917, PMID: 27894351, PMID: 33726816, PMID: 23559409, PMID: 26673778, PMID: 30002499, PMID: 33323469), 12 were homozygotes (PMID: 32055034, PMID: 32552793, PMID: 27894351, PMID: 18371931, PMID: 20007846) and 4 were compound heterozygotes who carried pathogenic or likely pathogenic variants in trans (PMID: 33532864, ClinVar Variation ID: 659899; PMID: 28973083, ClinVar Variation ID: 988261; PMID: 23559409, ClinVar Variation ID: 96511, ClinVar Variation ID: 693989 ; PMID: 30002499, ClinVar Variation ID: 262696; PMID: 33323469, ClinVar Variation ID: 1454640), which increases the likelihood that the c.2694-2_2694-1del variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 220868) and has been interpreted as pathogenic by multiple submitters. RT-PCR analysis performed on affected tissue shows evidence of altered splicing of exon 20 (PMID: 32552793, PMID: 30002499, PMID: 20007846). A different nucleotide change that also results in a splice acceptor variant at the same site, c.2694-2A>T (ClinVar Variation ID: 1524627), has been previously reported likely pathogenic, and the variant being assessed here, c.2694-2_2694-1del, is predicted by SpliceAI to have a similar effect on splicing. This variant is located in the 3' splice region. Computational tools do suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. There is an in-frame cryptic splice site 21 bases from the intron-exon boundary, providing evidence that this variant may delete 7 amino acids instead of causing loss of function. However, this information is not predictive enough to determine pathogenicity. Loss of function of the NPHP3 gene is an established disease mechanism in autosomal recessive renal-hepatic-pancreatic dysplasia 1. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive renal-hepatic-pancreatic dysplasia 1. ACMG/AMP Criteria applied: PVS1_Moderate, PS1_Supporting, PS3_Moderate, PM3_VeryStrong (Richards 2015).
Comment:
This sequence change affects a splice site in intron 19 of the NPHP3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs751527253, gnomAD 0.05%). Disruption of this splice site has been observed in individual(s) with Meckel-Gruber-like syndrome and/or nephronophthisis-related ciliopathy (PMID: 18371931, 20007846, 23559409, 26673778). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 220868). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 20007846). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PS3,PM2.
Comment:
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0002759, PM2).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000220868.16). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
The splice site c.2694-2_2694-1del variant has been reported to segregate with Meckel syndrome and embryonic lethality in families (Bergmann et. al., 2008). An experimental study has shown that this variant results in altered splicing, likely by usage of a cryptic splice site, resulting in a prematurely truncated protein (Fiskerstrand et. al., 2010). The c.2694-2_2694-1del variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.02759% in gnomAD database. This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (Baralle D, Baralle M., 2005), and loss-of-function variants in NPHP3 are known to be pathogenic (Halbritter et. al., 2013). For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed. The same variant (c.2694-2_2694-1del) has been observed in her father.
Comment:
PVS1,PM2_p
Comment:
NPHP3: PVS1, PS3:Supporting, PS4:Supporting
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Meckel syndrome 7 (MIM# 267010), nephronophthisis 3 (MIM# 604387) and renal-hepatic-pancreatic dysplasia 1 (MIM# 208540). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0210 - Splice site variant proven to affect splicing of the transcript with a known effect on protein sequence. RT-PCR done on whole blood RNA of an affected individual demonstrated exon 20 skipping, which is expected to result in a frameshift (PMID: 30002499). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 78 heterozygotes, 0 homozygotes). (SP) 0311 - An alternative nucleotide change at the same canonical splice site is present in gnomAD (v3: 1 heterozygote, 0 homozygotes). (SB) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten individuals described to have nephronophthisis, end stage renal disease or ciliopathy syndrome and consistently classified as pathogenic by diagnostic laboratories in ClinVar (PMID: 28921755, 30002499, 32055034). (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
The heterozygous c.2694-2_2694-1delAG variant was identified by our study in the compound heterozygous state, with a pathogenic variant, in one individual with nephronophthisis. This variant is pathogenic based off of multiple reports in ClinVar and the literature.
Comment:
The NPHP3 c.2694-2_2694-1delAG variant is predicted to result in a deletion affecting a canonical splice site. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with NPHP3 related disorders (Bergmann et al. 2008. PubMed ID: 18371931; Meng et al 2017. PubMed ID: 28973083; Shaheen et al 2016. PubMed ID: 27894351; Shamseldin et al. 2021. PubMed ID: 34645488). Expression assays reveal that this variant leads to skipping of exon 20 (Maddirevula et al. 2020. PubMed ID: 32552793). This variant is reported in 0.046% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players. | Domingo-Gallego A | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2022 | PMID: 33532864 |
| Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics. | Maddirevula S | Genome biology | 2020 | PMID: 32552793 |
| The morbid genome of ciliopathies: an update. | Shamseldin HE | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32055034 |
| Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. | Hou YC | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31980526 |
| Human urine-derived renal epithelial cells provide insights into kidney-specific alternate splicing variants. | Molinari E | European journal of human genetics : EJHG | 2018 | PMID: 30002499 |
| Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. | Meng L | JAMA pediatrics | 2017 | PMID: 28973083 |
| Homozygous mutation in the NPHP3 gene causing foetal nephronophthisis. | Abdullah U | Nephrology (Carlton, Vic.) | 2017 | PMID: 28921755 |
| Characterizing the morbid genome of ciliopathies. | Shaheen R | Genome biology | 2016 | PMID: 27894351 |
| Large-scale targeted sequencing comparison highlights extreme genetic heterogeneity in nephronophthisis-related ciliopathies. | Schueler M | Journal of medical genetics | 2016 | PMID: 26673778 |
| Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
| Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy. | Halbritter J | Human genetics | 2013 | PMID: 23559409 |
| Identification of a gene for renal-hepatic-pancreatic dysplasia by microarray-based homozygosity mapping. | Fiskerstrand T | The Journal of molecular diagnostics : JMD | 2010 | PMID: 20007846 |
| Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. | Bergmann C | American journal of human genetics | 2008 | PMID: 18371931 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NPHP3 | - | - | - | - |
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Text-mined citations for rs751527253 ...
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Record last updated Nov 25, 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.