VCV000546087.33 - ClinVar

NM_001009944.3(PKD1):c.8932TTC[1] (p.Phe2979del)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001009944.3(PKD1):c.8932TTC[1] (p.Phe2979del)

Variation ID: 546087 Accession: VCV000546087.33

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: 16p13.3 16: 2102825-2102827 (GRCh38) [ NCBI UCSC ] 16: 2152826-2152828 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 9, 2018	Oct 20, 2024	Jun 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001009944.3:c.8932TTC[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001009944.3:p.Phe2979del	inframe deletion
NM_001009944.3:c.8935_8937del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000296.3:c.8935_8937delTTC
NM_000296.4:c.8932TTC[1]	NP_000287.4:p.Phe2979del	inframe deletion
NM_001009944.2:c.8935_8937del
NC_000016.10:g.2102826AAG[1]
NC_000016.9:g.2152827AAG[1]
NG_008617.1:g.40391TTC[1]

... more HGVS ... less HGVS

Protein change

F2979del

Other names

p.2979_2979del

Canonical SPDI

NC_000016.10:2102824:GAAGAAG:GAAG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbSNP: rs1358948221 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PKD1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	3777	4362
MIR6511B1	-	-	-	GRCh38	-	31

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Likely pathogenic (4)	criteria provided, multiple submitters, no conflicts	Feb 2, 2023	RCV000657874.22
Polycystic kidney disease, adult type	Likely pathogenic (4)	criteria provided, multiple submitters, no conflicts	Aug 22, 2023	RCV001095616.8
Inborn genetic diseases	Likely pathogenic (1)	criteria provided, single submitter	Jan 5, 2024	RCV004026019.1
Autosomal dominant polycystic kidney disease	Likely pathogenic (1)	criteria provided, single submitter	Jun 5, 2024	RCV004760681.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Feb 05, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Polycystic kidney disease, adult type (Autosomal dominant inheritance) Affected status: yes Allele origin: unknown	Cavalleri Lab, Royal College of Surgeons in Ireland Accession: SCV001251253.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: PM2, PM4, PP4, PP5 Clinical Features: Polycystic kidney dysplasia (present)
Likely pathogenic (May 16, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Polycystic kidney disease, adult type Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV001752650.2 First in ClinVar: Jul 18, 2021 Last updated: Dec 31, 2022
Likely pathogenic (Feb 02, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000779635.5 First in ClinVar: Jul 09, 2018 Last updated: Nov 11, 2023	Comment: In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a … (more) In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11571556, 31740684, 33454723, 17582161, 27499327) (less)
Likely pathogenic (Aug 22, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Polycystic kidney disease, adult type (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV004027841.1 First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023	Comment: heterozygous variant identified in a 36 year old turkish female of consanguineous parents; patient suffored from multiple renal cysts and polycystic kidney prevalent in family … (more) heterozygous variant identified in a 36 year old turkish female of consanguineous parents; patient suffored from multiple renal cysts and polycystic kidney prevalent in family history; variant causes in-frame deletion of 1 amino acid in a non-repeat region of PKD1 (less) Clinical Features: Polycystic kidney disease (present) , Multiple renal cysts (present)
Likely pathogenic (Jan 05, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV005005810.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Publications: PubMed (7) PubMed: 11571556‚ 17582161‚ 27499327‚ 31740684‚ 32457805‚ 33315352‚ 33454723 Comment: The c.8935_8937delTTC (p.F2979del) alteration is located in exon 24 (coding exon 24) of the PKD1 gene. This alteration consists of an in-frame deletion of 3 … (more) The c.8935_8937delTTC (p.F2979del) alteration is located in exon 24 (coding exon 24) of the PKD1 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.8935 and c.8937, resulting in the deletion of <NA> residues. This allele was reported in one heterozygous individual in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been detected in the heterozygous state in multiple individuals with clinical features of PKD1-related polycystic kidney disease (Kasap, 2021; Mantovani, 2020; Kim, 2019; Carrera, 2016; Rossetti, 2007; Bouba, 2001; Benson, 2021; external communication). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as likely pathogenic. (less)
Likely pathogenic (Jun 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Autosomal dominant polycystic kidney disease Affected status: yes Allele origin: germline	Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research Accession: SCV005373720.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024	Method: Whole Genome Sequencing
Likely pathogenic (Jul 01, 2021)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002563288.16 First in ClinVar: Aug 23, 2022 Last updated: Oct 20, 2024	Number of individuals with the variant: 2
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002033921.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002036321.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Likely pathogenic (Oct 09, 2023)	no assertion criteria provided Method: clinical testing	Polycystic kidney disease, adult type Affected status: yes Allele origin: germline	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas Accession: SCV004041634.1 First in ClinVar: Oct 14, 2023 Last updated: Oct 14, 2023

Comment:

In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11571556, 31740684, 33454723, 17582161, 27499327)

Comment:

heterozygous variant identified in a 36 year old turkish female of consanguineous parents; patient suffored from multiple renal cysts and polycystic kidney prevalent in family history; variant causes in-frame deletion of 1 amino acid in a non-repeat region of PKD1

Comment:

The c.8935_8937delTTC (p.F2979del) alteration is located in exon 24 (coding exon 24) of the PKD1 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.8935 and c.8937, resulting in the deletion of <NA> residues. This allele was reported in one heterozygous individual in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been detected in the heterozygous state in multiple individuals with clinical features of PKD1-related polycystic kidney disease (Kasap, 2021; Mantovani, 2020; Kim, 2019; Carrera, 2016; Rossetti, 2007; Bouba, 2001; Benson, 2021; external communication). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as likely pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The genetic landscape of polycystic kidney disease in Ireland.	Benson KA	European journal of human genetics : EJHG	2021	PMID: 33454723
Demographic and clinical characteristics of children with autosomal dominant polycystic kidney disease: a single center experience.	Kasap Demir B	Turkish journal of medical sciences	2021	PMID: 33315352
Gene Panel Analysis in a Large Cohort of Patients With Autosomal Dominant Polycystic Kidney Disease Allows the Identification of 80 Potentially Causative Novel Variants and the Characterization of a Complex Genetic Architecture in a Subset of Families.	Mantovani V	Frontiers in genetics	2020	PMID: 32457805
Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing.	Kim H	Scientific reports	2019	PMID: 31740684
Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).	Carrera P	Scientific reports	2016	PMID: 27499327
Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease.	Rossetti S	Journal of the American Society of Nephrology : JASN	2007	PMID: 17582161
Novel PKD1 deletions and missense variants in a cohort of Hellenic polycystic kidney disease families.	Bouba I	European journal of human genetics : EJHG	2001	PMID: 11571556

Text-mined citations for rs1358948221 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001009944.3(PKD1):c.8932TTC[1] (p.Phe2979del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1358948221 ...