NM_000297.4(PKD2):c.709+1G>A AND Autosomal dominant polycystic kidney disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 24, 2023
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:: RCV003584550.3

Allele description [Variation Report for NM_000297.4(PKD2):c.709+1G>A]

NM_000297.4(PKD2):c.709+1G>A

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.709+1G>A

HGVS:

NC_000004.12:g.88019572G>A
NG_008604.1:g.16905G>A
NM_000297.4:c.709+1G>AMANE SELECT
NC_000004.11:g.88940724G>A
NM_000297.3:c.709+1G>A

Links:

dbSNP: rs398123308

NCBI 1000 Genomes Browser:

rs398123308

Molecular consequence:

NM_000297.4:c.709+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Autosomal dominant polycystic kidney disease (ADPKD)
Identifiers:: MONDO: MONDO:0004691; MedGen: C0085413

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293199	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 24, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9326320, 26453610, 27499327, 33437033, 16199547, 17582161, 22863349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293199

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 24, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2).

Veldhuisen B, Saris JJ, de Haij S, Hayashi T, Reynolds DM, Mochizuki T, Elles R, Fossdal R, Bogdanova N, van Dijk MA, Coto E, Ravine D, Nørby S, Verellen-Dumoulin C, Breuning MH, Somlo S, Peters DJ.

Am J Hum Genet. 1997 Sep;61(3):547-55.

PubMed [citation]

PMID:: 9326320
PMCID:: PMC1715954

Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease.

Hwang YH, Conklin J, Chan W, Roslin NM, Liu J, He N, Wang K, Sundsbak JL, Heyer CM, Haider M, Paterson AD, Harris PC, Pei Y.

J Am Soc Nephrol. 2016 Jun;27(6):1861-8. doi: 10.1681/ASN.2015060648. Epub 2015 Oct 9.

PubMed [citation]

PMID:: 26453610
PMCID:: PMC4884120

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293199.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 92797). Disruption of this splice site has been observed in individual(s) with autosomal dominant polycystic kidney disease (PMID: 9326320, 26453610, 27499327, 33437033). This sequence change affects a donor splice site in intron 2 of the PKD2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKD2 are known to be pathogenic (PMID: 17582161, 22863349).

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

Last Updated: May 16, 2025

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