NM_001009944.3(PKD1):c.9898G>A (p.Gly3300Arg) AND Polycystic kidney disease, adult type

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Mar 25, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001171380.3

Allele description [Variation Report for NM_001009944.3(PKD1):c.9898G>A (p.Gly3300Arg)]

NM_001009944.3(PKD1):c.9898G>A (p.Gly3300Arg)

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.9898G>A (p.Gly3300Arg)
HGVS:
  • NC_000016.10:g.2099886C>T
  • NG_008617.1:g.43335G>A
  • NM_000296.4:c.9898G>A
  • NM_001009944.3:c.9898G>AMANE SELECT
  • NP_000287.4:p.Gly3300Arg
  • NP_001009944.3:p.Gly3300Arg
  • NC_000016.9:g.2149887C>T
  • NM_001009944.2:c.9898G>A
  • p.G3300R
Protein change:
G3300R
Links:
dbSNP: rs777024498
NCBI 1000 Genomes Browser:
rs777024498
Molecular consequence:
  • NM_000296.4:c.9898G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001009944.3:c.9898G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
no known functional consequence
Observations:
3

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
SCV001250666University of Iowa Renal Genetics Clinic,University of Iowacriteria provided, single submitter
Likely benign
(Mar 25, 2020)
germlineclinical testing

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

SCV001472254ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Jan 30, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Caucasiangermlineno1not providednot providednot providednot providedclinical testing
Caucasian germlineyes2not 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 University of Iowa Renal Genetics Clinic,University of Iowa, SCV001250666.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian1not providednot providedclinical testing PubMed (1)
2Caucasian1not providednot providedclinical testing PubMed (1)
3Caucasian1not providednot providedclinical testing PubMed (1)

Description

Segregation analysis of the Gly3300Arg variant in an unaffected family member provides evidence this variant now meets ACMG pathogenicity criteria BS4 and BP5 and is therefore classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided
2germlinenonot providednot providednot provided1not providednot providednot provided
3germlineyesnot providednot providednot provided1not providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001472254.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The PKD1 c.9898G>A; p.Gly3300Arg variant (rs777024498) is reported in the literature in at least one individual affected with autosomal dominant polycystic kidney disease (Cornec-Le Gall 2013). This variant is reported in ClinVar (Variation ID: 427112), and is found in the general population with an overall allele frequency of 0.012% (24/197542 alleles) in the Genome Aggregation Database. The glycine at codon 3300 is highly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Gly3300Arg variant is uncertain at this time References: Cornec-Le Gall E et al. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol. 2013 May;24(6):1006-13.

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

Last Updated: Nov 27, 2021

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