NM_138694.4(PKHD1):c.10444C>T (p.Arg3482Cys) AND Autosomal recessive polycystic kidney disease

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 4, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000169255.7

Allele description [Variation Report for NM_138694.4(PKHD1):c.10444C>T (p.Arg3482Cys)]

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

Gene:
PKHD1:PKHD1 ciliary IPT domain containing fibrocystin/polyductin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p12.3
Genomic location:
Preferred name:
NM_138694.4(PKHD1):c.10444C>T (p.Arg3482Cys)
HGVS:
  • NC_000006.12:g.51659682G>A
  • NG_008753.1:g.432944C>T
  • NM_138694.4:c.10444C>TMANE SELECT
  • NP_619639.3:p.Arg3482Cys
  • NC_000006.11:g.51524480G>A
  • NM_138694.3:c.10444C>T
  • P08F94:p.Arg3482Cys
Protein change:
R3482C
Links:
UniProtKB: P08F94#VAR_018591; dbSNP: rs148617572
NCBI 1000 Genomes Browser:
rs148617572
Molecular consequence:
  • NM_138694.4:c.10444C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive polycystic kidney disease (ARPKD)
Synonyms:
POLYCYSTIC KIDNEY AND HEPATIC DISEASE 1; POLYCYSTIC KIDNEY DISEASE, INFANTILE, TYPE I; Polycystic kidney disease, infantile type; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009889; MedGen: C0085548; Orphanet: 731; Orphanet: 8378

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000220543Counsylcriteria provided, single submitter
Likely pathogenic
(Jul 23, 2014)
unknownliterature only

PubMed (4)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000754646Invitaecriteria provided, single submitter
Pathogenic
(Nov 4, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV000965800Equipe Genetique des Anomalies du Developpement, Université de Bourgognecriteria provided, single submitter
Likely pathogenic
(Jan 1, 2014)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001163015Baylor Geneticscriteria provided, single submitter
Pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

Denamur E, Delezoide AL, Alberti C, Bourillon A, Gubler MC, Bouvier R, Pascaud O, Elion J, Grandchamp B, Michel-Calemard L, Missy P, Zaccaria I, Le Nagard H, Gerard B, Loirat C; Société Française de Foetopathologie., Barbet J, Beaufrère AM, Berchel C, Bessières B, Boudjemaa S, Buenerd A, et al.

Kidney Int. 2010 Feb;77(4):350-8. doi: 10.1038/ki.2009.440. Epub 2009 Nov 25.

PubMed [citation]
PMID:
19940839

Spectrum of mutations in the gene for autosomal recessive polycystic kidney disease (ARPKD/PKHD1).

Bergmann C, Senderek J, Sedlacek B, Pegiazoglou I, Puglia P, Eggermann T, Rudnik-Schöneborn S, Furu L, Onuchic LF, De Baca M, Germino GG, Guay-Woodford L, Somlo S, Moser M, Büttner R, Zerres K.

J Am Soc Nephrol. 2003 Jan;14(1):76-89.

PubMed [citation]
PMID:
12506140
See all PubMed Citations (9)

Details of each submission

From Counsyl, SCV000220543.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000754646.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

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 large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs148617572, ExAC 0.02%). This variant has been reported in individuals affected with autosomal recessive polycystic kidney disease and related conditions (PMID: 12506140, 15108281, 15805161, 26385851, 26721323). ClinVar contains an entry for this variant (Variation ID: 188896). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000965800.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV001163015.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 27, 2021

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