NM_000297.4(PKD2):c.1081C>T (p.Arg361Ter) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Sep 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000788690.30

Allele description [Variation Report for NM_000297.4(PKD2):c.1081C>T (p.Arg361Ter)]

NM_000297.4(PKD2):c.1081C>T (p.Arg361Ter)

Gene:

PKD2:polycystin 2, transient receptor potential cation channel [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q22.1

Genomic location:

Preferred name:

NM_000297.4(PKD2):c.1081C>T (p.Arg361Ter)

HGVS:

NC_000004.12:g.88038488C>T
NG_008604.1:g.35821C>T
NM_000297.4:c.1081C>TMANE SELECT
NP_000288.1:p.Arg361Ter
NC_000004.11:g.88959640C>T
NM_000297.3:c.1081C>T
NR_156488.2:n.1180C>T

Protein change:

R361*

Links:

dbSNP: rs1578130676

NCBI 1000 Genomes Browser:

rs1578130676

Molecular consequence:

NR_156488.2:n.1180C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000297.4:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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MAG: Exodeoxyribonuclease 7 small subunit [SAR92 bacterium MED-G29]
MAG: Exodeoxyribonuclease 7 small subunit [SAR92 bacterium MED-G29]
gi|2476646616|emb|CAI8258674.1||gnl CATI|CAI8258674

Protein
uncharacterized protein MONBRDRAFT_20766, partial [Monosiga brevicollis MX1]
uncharacterized protein MONBRDRAFT_20766, partial [Monosiga brevicollis MX1]
gi|167521624|ref|XP_001745150.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000927887	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Aug 28, 2018)	germline	clinical testing	Citation Link,
SCV001250327	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2019)	germline	clinical testing	Citation Link,
SCV001782674	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 1, 2023)	germline	clinical testing	Citation Link,
SCV003839866	Genetic Services Laboratory, University of Chicago	no assertion criteria provided	Pathogenic (Sep 2, 2022)	germline	clinical testing

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Summary from all submissions

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

Details of each submission

From Blueprint Genetics, SCV000927887.1

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

#	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		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001250327.26

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

#	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

From GeneDx, SCV001782674.2

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30215095, 27782177, 30816285, 23376035, 25525159, 17100995, 22508176, 22863349, 31740684, 33168999, 33726816, 34101167, 33141305, 35478332)

#	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		not provided	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV003839866.1

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

Description

DNA sequence analysis of the PKD2 gene demonstrated a sequence change, c.1081C>T, which results in the creation of a premature stop codon at amino acid position 361, p.Arg361*. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated PKD2 protein with potentially abnormal function. This sequence change has not been described in population databases such as ExAC and gnomAD. This pathogenic sequence change has previously been described in multiple individuals with autosomal dominant polycystic kidney disease (PMID: 34101167, 30816285, 33141305, 31740684, 27782177, 17100995, 22508176). Based on these collective evidences, this sequence change is classified as pathogenic.

#	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		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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