NM_138694.4(PKHD1):c.10561C>T (p.Gln3521Ter) AND Autosomal recessive polycystic kidney disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 21, 2020
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:: RCV001387380.7

Allele description [Variation Report for NM_138694.4(PKHD1):c.10561C>T (p.Gln3521Ter)]

NM_138694.4(PKHD1):c.10561C>T (p.Gln3521Ter)

Gene:

PKHD1:PKHD1 ciliary IPT domain containing fibrocystin/polyductin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p12.3

Genomic location:

Preferred name:

NM_138694.4(PKHD1):c.10561C>T (p.Gln3521Ter)

HGVS:

NC_000006.12:g.51659565G>A
NG_008753.1:g.433061C>T
NM_138694.4:c.10561C>TMANE SELECT
NP_619639.3:p.Gln3521Ter
NC_000006.11:g.51524363G>A

Protein change:

Q3521*

Links:

dbSNP: rs2150415240

NCBI 1000 Genomes Browser:

rs2150415240

Molecular consequence:

NM_138694.4:c.10561C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Autosomal recessive polycystic kidney disease (ARPKD)
Synonyms:: POLYCYSTIC KIDNEY AND HEPATIC DISEASE 1; POLYCYSTIC KIDNEY DISEASE, INFANTILE, TYPE I; Polycystic kidney disease, infantile type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009889; MeSH: D017044; MedGen: C0085548; Orphanet: 731; Orphanet: 8378

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587996	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 21, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19940839, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001587996

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 21, 2020)

germline

clinical testing

PubMed (2)
[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

Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

Denamur E, Delezoide AL, Alberti C, Bourillon A, Gubler MC, Bouvier R, Pascaud O, Elion J, Grandchamp B, Michel-Calemard L, Missy P, Zaccaria I, Le Nagard H, Gerard B, Loirat C; Société Française de Foetopathologie., Barbet J, Beaufrère AM, Berchel C, Bessières B, Boudjemaa S, Buenerd A, et al.

Kidney Int. 2010 Feb;77(4):350-8. doi: 10.1038/ki.2009.440. Epub 2009 Nov 25.

PubMed [citation]

PMID:: 19940839

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, SCV001587996.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant has not been reported in the literature in individuals with PKHD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln3521*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product.

#	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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