NM_000297.4(PKD2):c.203dup (p.Ala69fs) AND Polycystic kidney disease 2

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 24, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002289770.3

Allele description [Variation Report for NM_000297.4(PKD2):c.203dup (p.Ala69fs)]

NM_000297.4(PKD2):c.203dup (p.Ala69fs)

Genes:

LOC129992813:ATAC-STARR-seq lymphoblastoid silent region 15559 [Gene]
PKD2:polycystin 2, transient receptor potential cation channel [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

4q22.1

Genomic location:

Preferred name:

NM_000297.4(PKD2):c.203dup (p.Ala69fs)

HGVS:

NC_000004.12:g.88007936dup
NG_008604.1:g.5269dup
NM_000297.4:c.203dupMANE SELECT
NP_000288.1:p.Ala69fs
NC_000004.11:g.88929082_88929083insC
NC_000004.11:g.88929088dup
NM_000297.3:c.203dup
NM_000297.3:c.203dupC
NR_156488.2:n.302dup

Protein change:

A69fs

Links:

OMIM: 173910.0007; dbSNP: rs1187336837

NCBI 1000 Genomes Browser:

rs1187336837

Molecular consequence:

NM_000297.4:c.203dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_156488.2:n.302dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Polycystic kidney disease 2 (PKD2)
Synonyms:: POLYCYSTIC KIDNEY DISEASE, ADULT, TYPE II; POLYCYSTIC KIDNEY DISEASE 2 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE
Identifiers:: MONDO: MONDO:0013131; MedGen: C2751306; OMIM: 613095

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034729	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1999)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002580810	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000034729

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 1999)

germline

literature only

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

SCV002580810

MGZ Medical Genetics Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 24, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease.

Koptides M, Hadjimichael C, Koupepidou P, Pierides A, Constantinou Deltas C.

Hum Mol Genet. 1999 Mar;8(3):509-13.

PubMed [citation]

PMID:: 9949210

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 OMIM, SCV000034729.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 7 of 21 cysts from both kidneys of a patient with polycystic kidney disease (PKD2; 613095), Koptides et al. (1999) identified a C insertion within the inherited wildtype PKD2 allele. This C insertion was different from the one previously identified (693insC; 173910.0004) in this family as the germline mutation. The insertion occurred within a sequence of 6 consecutive cytosines (nucleotides 197-203), encoding amino acids 66-68. The authors were unable to determine exactly where the insertion of the cytosine occurred. The mutation was expected to create a translation frameshift, leading to the incorporation of 22 novel amino acids before reaching a stop codon. A polymorphism at nucleotide 83, which was occupied by either G or C, encoding either arginine or proline, enabled Koptides et al. (1999) to verify that the C insertion had occurred in the inherited wildtype allele.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From MGZ Medical Genetics Center, SCV002580810.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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