NM_000297.4(PKD2):c.65_66delinsTT (p.Arg22Leu) AND Autosomal dominant polycystic kidney disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 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:: RCV003747135.3

Allele description [Variation Report for NM_000297.4(PKD2):c.65_66delinsTT (p.Arg22Leu)]

NM_000297.4(PKD2):c.65_66delinsTT (p.Arg22Leu)

Genes:

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

Variant type:

Indel

Cytogenetic location:

4q22.1

Genomic location:

Preferred name:

NM_000297.4(PKD2):c.65_66delinsTT (p.Arg22Leu)

HGVS:

NC_000004.12:g.88007798_88007799delinsTT
NG_008604.1:g.5131_5132delinsTT
NG_172259.1:g.501_502delinsTT
NM_000297.4:c.65_66delinsTTMANE SELECT
NP_000288.1:p.Arg22Leu
NC_000004.11:g.88928950_88928951delinsTT
NR_156488.2:n.164_165delinsTT

Protein change:

R22L

Molecular consequence:

NM_000297.4:c.65_66delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NR_156488.2:n.164_165delinsTT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004491444	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 13, 2023)	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

SCV004491444

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 13, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004491444.1

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

Description

This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 22 of the PKD2 protein (p.Arg22Leu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with PKD2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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