NM_001009944.3:c.840_845delTGTGTG

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001009944.3(PKD1):c.*840_*845delTGTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 421,114 control chromosomes in the GnomAD database, including 1,639 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.072 ( 490 hom., cov: 0)

Exomes 𝑓: 0.084 ( 1149 hom. )

Consequence

PKD1
NM_001009944.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.411

Publications

1 publications found

Variant links:

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

PKD1 links:

TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]

TSC2 Gene-Disease associations (from GenCC):

tuberous sclerosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
tuberous sclerosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
lymphangioleiomyomatosis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tuberous sclerosis complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TSC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 16-2088881-GCACACA-G is Benign according to our data. Variant chr16-2088881-GCACACA-G is described in ClinVar as [Benign]. Clinvar id is 1049696.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.840_845delTGTGTG		3_prime_UTR_variant	Exon 46 of 46	ENST00000262304.9	NP_001009944.3
TSC2	NM_000548.5 link	c.284_289delCACACA		3_prime_UTR_variant	Exon 42 of 42	ENST00000219476.9	NP_000539.2	P49815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.840_845delTGTGTG		3_prime_UTR_variant	Exon 46 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1
TSC2	ENST00000219476.9 link	c.284_289delCACACA		3_prime_UTR_variant	Exon 42 of 42	5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

10514

AN:

146582

Hom.:

492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.0476

Gnomad AMR

AF:

0.0592

Gnomad ASJ

AF:

0.0958

Gnomad EAS

AF:

0.000976

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0903

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0767

GnomAD4 exome

AF:

0.0839

AC:

23032

AN:

274428

Hom.:

1149

AF XY:

0.0816

AC XY:

11834

AN XY:

145024

show subpopulations

African (AFR)

AF:

0.0197

AC:

142

AN:

7200

American (AMR)

AF:

0.0548

AC:

552

AN:

10076

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

881

AN:

8414

East Asian (EAS)

AF:

0.000214

AC:

AN:

18718

South Asian (SAS)

AF:

0.0565

AC:

2043

AN:

36188

European-Finnish (FIN)

AF:

0.0869

AC:

1220

AN:

14034

Middle Eastern (MID)

AF:

0.107

AC:

117

AN:

1090

European-Non Finnish (NFE)

AF:

0.102

AC:

16694

AN:

163242

Other (OTH)

AF:

0.0892

AC:

1379

AN:

15466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

937

1873

2810

3746

4683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0716

AC:

10509

AN:

146686

Hom.:

490

Cov.:

AF XY:

0.0698

AC XY:

5008

AN XY:

71742

show subpopulations

African (AFR)

AF:

0.0198

AC:

743

AN:

37482

American (AMR)

AF:

0.0591

AC:

884

AN:

14950

Ashkenazi Jewish (ASJ)

AF:

0.0958

AC:

328

AN:

3424

East Asian (EAS)

AF:

0.000978

AC:

AN:

5112

South Asian (SAS)

AF:

0.0554

AC:

265

AN:

4786

European-Finnish (FIN)

AF:

0.109

AC:

1123

AN:

10338

Middle Eastern (MID)

AF:

0.0833

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.103

AC:

6939

AN:

67358

Other (OTH)

AF:

0.0758

AC:

155

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

476

952

1427

1903

2379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0286

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 12, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001009944.3:c.840_845delTGTGTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over