NM_001009944.3(PKD1):c.7927C>T (p.Arg2643Cys) AND Polycystic kidney disease, adult type

Clinical significance:Pathogenic (Last evaluated: Feb 4, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001252966.2

Allele description [Variation Report for NM_001009944.3(PKD1):c.7927C>T (p.Arg2643Cys)]

NM_001009944.3(PKD1):c.7927C>T (p.Arg2643Cys)

Gene:
PKD1:polycystin 1, transient receptor potential channel interacting [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_001009944.3(PKD1):c.7927C>T (p.Arg2643Cys)
HGVS:
  • NC_000016.10:g.2105411G>A
  • NG_008617.1:g.35488C>T
  • NM_000296.4:c.7927C>T
  • NM_001009944.3:c.7927C>TMANE SELECT
  • NP_000287.4:p.Arg2643Cys
  • NP_001009944.3:p.Arg2643Cys
  • NC_000016.9:g.2155412G>A
  • NM_001009944.2:c.7927C>T
Protein change:
R2643C
Molecular consequence:
  • NM_000296.4:c.7927C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001009944.3:c.7927C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Polycystic kidney disease, adult type (PKD1)
Synonyms:
Polycystic Kidney, Autosomal Dominant; POLYCYSTIC KIDNEY DISEASE, ADULT, TYPE I; Polycystic kidney disease 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008263; MedGen: C3149841; OMIM: 173900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001427176Victorian Clinical Genetics Services,Murdoch Childrens Research Institutecriteria provided, single submitter
Pathogenic
(Feb 4, 2019)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Victorian Clinical Genetics Services,Murdoch Childrens Research Institute, SCV001427176.2

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

Description

A heterozygous missense variant, NM_001009944.2(PKD1):c.7927C>T, has been identified in exon 21 of 46 of the PKD1 gene. The variant is predicted to result in a major amino acid change from arginine to cysteine at position 2643 of the protein (NP_001009944.2(PKD1):p.(Arg2643Cys)). The arginine at this position has high conservation (100 vertebrates, UCSC), and is located within the GPCR-autoproteolysis inducing (Arac, D. et al., 2012) functional domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.0004% (1 heterozygote). An alternative residue change has been reported in the gnomAD database at a frequency of 0.008%. The variant has been previously described as pathogenic in patients with autosomal dominant polycystic kidney disease (ADPKD) (Garcia-Gonzalez, M.A. et al., 2007; Mallawaarachchi, A.C. et al., 2016). Additionally, studies showed that this variant impacts protein function (Garcia-Gonzalez, M.A. et al., 2007). Despite analysis of maternal sample, the inheritance of this variant remains unsolved. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

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

Last Updated: Oct 7, 2021

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