NM_001009944.3(PKD1):c.12391_12393del (p.Glu4131del) AND Polycystic kidney disease

Clinical significance:Likely pathogenic

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000500794.2

Allele description [Variation Report for NM_001009944.3(PKD1):c.12391_12393del (p.Glu4131del)]

NM_001009944.3(PKD1):c.12391_12393del (p.Glu4131del)

Gene:
PKD1:polycystin 1, transient receptor potential channel interacting [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_001009944.3(PKD1):c.12391_12393del (p.Glu4131del)
HGVS:
  • NC_000016.10:g.2090337_2090339del
  • NG_005895.1:g.46032_46034del
  • NG_008617.1:g.52883_52885del
  • NM_000296.4:c.12388_12390del
  • NM_001009944.3:c.12391_12393delMANE SELECT
  • NP_000287.4:p.Glu4130del
  • NP_001009944.3:p.Glu4131del
  • LRG_487:g.46032_46034del
  • NC_000016.9:g.2140338_2140340del
  • NM_000296.3:c.12388_12390del
  • NM_001009944.2:c.12391_12393del
  • NM_001009944.2:c.12391_12393delGAG
Protein change:
E4130del
Links:
dbSNP: rs1555444468
NCBI 1000 Genomes Browser:
rs1555444468
Molecular consequence:
  • NM_000296.4:c.12388_12390del - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001009944.3:c.12391_12393del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:
Polycystic kidney disease
Synonyms:
Polycystic kidney dysplasia; Enlarged polycystic kidneys; Polycystic kidneys
Identifiers:
MONDO: MONDO:0020642; MedGen: C0022680; OMIM: PS173900; Human Phenotype Ontology: HP:0000113

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000592863Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedLikely pathogenicunknownclinical testing

Summary from all submissions

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

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592863.3

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

Description

The PKD1 p.Glu4131del variant was identified in the literature in 1 of 440 proband chromosomes (freq. 0.002) in a study determining the genotype-phenotype relationship of ADPKD variants; control chromosomes were not tested (Hwang 2016). The same study reported that this variant segregated in 5 or more disease-informative family members (positive and affected, or negative, unaffected, and over 40 years of age). The variant was also identified in ClinVar (our laboratory was the only submitter) and ADPKD Mutation Database (classified as likely pathogenic). The variant was not identified in dbSNP, LOVD 3.0, PKD1-LOVD, the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). This variant is an in-frame deletion resulting in the removal of a Glutamic acid (Glu) residue at codon 4131; the impact of this alteration on PKD1 protein function is not known. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.

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

Last Updated: Oct 8, 2021

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