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NM_138694.4(PKHD1):c.10444C>T (p.Arg3482Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Aug 20, 2021)
Last evaluated:
Nov 7, 2019
Accession:
VCV000188896.7
Variation ID:
188896
Description:
single nucleotide variant
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NM_138694.4(PKHD1):c.10444C>T (p.Arg3482Cys)

Allele ID
186706
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
6p12.3
Genomic location
6: 51659682 (GRCh38) GRCh38 UCSC
6: 51524480 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000006.11:g.51524480G>A
NC_000006.12:g.51659682G>A
NM_138694.4:c.10444C>T MANE Select NP_619639.3:p.Arg3482Cys missense
... more HGVS
Protein change
R3482C
Other names
-
Canonical SPDI
NC_000006.12:51659681:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00005
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00006
Links
ClinGen: CA274092
UniProtKB: P08F94#VAR_018591
dbSNP: rs148617572
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Nov 4, 2019 RCV000169255.7
Pathogenic 2 criteria provided, single submitter Aug 5, 2016 RCV000726420.2
Pathogenic 1 criteria provided, single submitter Nov 7, 2019 RCV001331692.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PKHD1 - - GRCh38
GRCh37
2516 2532

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jul 23, 2014)
criteria provided, single submitter
Method: literature only
Polycystic kidney disease, infantile type
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000220543.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (4)
Pathogenic
(Aug 05, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000344513.4
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (4)
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Jan 01, 2014)
criteria provided, single submitter
Method: clinical testing
Polycystic kidney disease 4
Allele origin: germline
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000965800.1
Submitted: (Apr 26, 2017)
Evidence details
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Polycystic kidney disease 4
Allele origin: germline
Baylor Genetics
Accession: SCV001163015.1
Submitted: (Sep 27, 2019)
Evidence details
Pathogenic
(Nov 07, 2019)
criteria provided, single submitter
Method: clinical testing
Polycystic kidney disease 4
Allele origin: unknown
Baylor Genetics
Accession: SCV001523788.1
Submitted: (Feb 21, 2021)
Evidence details
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Pathogenic
(Nov 04, 2019)
criteria provided, single submitter
Method: clinical testing
Autosomal recessive polycystic kidney disease
Allele origin: germline
Invitae
Accession: SCV000754646.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with cysteine at codon 3482 of the PKHD1 protein (p.Arg3482Cys). The arginine residue is moderately conserved and there is a … (more)
Likely pathogenic
(Jun 24, 2019)
no assertion criteria provided
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001805444.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30275481, 19940839, … (more)

Functional evidence

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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

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Title Author Journal Year Link
An Ashkenazi founder mutation in the PKHD1 gene. Quint A European journal of medical genetics 2016 PMID: 26721323
Compound heterozygous PKHD1 variants cause a wide spectrum of ductal plate malformations. Courcet JB American journal of medical genetics. Part A 2015 PMID: 26385851
Novel Mutation in the PKHD1 Gene Diagnosed Prenatally in a Fetus with Autosomal Recessive Polycystic Kidney Disease. Thakur P Case reports in genetics 2014 PMID: 25114813
Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease. Denamur E Kidney international 2010 PMID: 19940839
Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts. Sharp AM Journal of medical genetics 2005 PMID: 15805161
PKHD1 mutations in families requesting prenatal diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Bergmann C Human mutation 2004 PMID: 15108281
Spectrum of mutations in the gene for autosomal recessive polycystic kidney disease (ARPKD/PKHD1). Bergmann C Journal of the American Society of Nephrology : JASN 2003 PMID: 12506140
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PKHD1 - - - -

Text-mined citations for rs148617572...

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These 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 Aug 27, 2021