16-2088881-GCACA-G

Position:

• chr16-2088881-GCACA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001009944.3(PKD1):​c.*842_*845del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 420,996 control chromosomes in the GnomAD database, including 950 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (279 hom., cov: 0)
  • Exomes 𝑓: 0.064 (671 hom.)
• Consequence: PKD1 NM_001009944.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-2088881-GCACA-G is Benign according to our data. Variant chr16-2088881-GCACA-G is described in ClinVar as [Benign]. Clinvar id is 1271867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5	c.*286_*289del		3_prime_UTR_variant	42/42	ENST00000219476.9	NP_000539.2
PKD1	NM_001009944.3	c.*842_*845del		3_prime_UTR_variant	46/46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9	c.*286_*289del		3_prime_UTR_variant	42/42	5	NM_000548.5	ENSP00000219476
PKD1	ENST00000262304.9	c.*842_*845del		3_prime_UTR_variant	46/46	1	NM_001009944.3	ENSP00000262304	P5

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8214 AN: 146596 Hom.: 279 Cov.: 0

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0144

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0387

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0484

GnomAD4 exome AF: 0.0641 AC: 17579 AN: 274296 Hom.: 671 AF XY: 0.0626 AC XY: 9072 AN XY: 144970

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.0342

Gnomad4 ASJ exome AF: 0.0897

Gnomad4 EAS exome AF: 0.00107

Gnomad4 SAS exome AF: 0.0547

Gnomad4 FIN exome AF: 0.0993

Gnomad4 NFE exome AF: 0.0729

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0560 AC: 8216 AN: 146700 Hom.: 279 Cov.: 0 AF XY: 0.0572 AC XY: 4107 AN XY: 71752

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0479

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs56279647; hg19: chr16-2138882;