chr16-2088881-G-GCGCACACA

Position:

• chr16-2088881-G-GCGCACACA

Variant summary

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

The NM_001009944.3(PKD1):​c.*845_*846insTGTGTGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (205 hom., cov: 0)
  • Exomes 𝑓: 0.014 (21 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-G-GCGCACACA is Benign according to our data. Variant chr16-2088881-G-GCGCACACA is described in ClinVar as [Benign]. Clinvar id is 1279025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5	c.*272_*273insGCACACAC		3_prime_UTR_variant	42/42	ENST00000219476.9	NP_000539.2
PKD1	NM_001009944.3	c.*845_*846insTGTGTGCG		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.*272_*273insGCACACAC		3_prime_UTR_variant	42/42	5	NM_000548.5	ENSP00000219476
PKD1	ENST00000262304.9	c.*845_*846insTGTGTGCG		3_prime_UTR_variant	46/46	1	NM_001009944.3	ENSP00000262304	P5

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 5930 AN: 146468 Hom.: 204 Cov.: 0

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.00885

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00752

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0356

GnomAD4 exome AF: 0.0139 AC: 3822 AN: 274468 Hom.: 21 Cov.: 0 AF XY: 0.0135 AC XY: 1952 AN XY: 145068

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.0163

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00663

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0405 AC: 5936 AN: 146572 Hom.: 205 Cov.: 0 AF XY: 0.0406 AC XY: 2908 AN XY: 71682

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.0272

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00753

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0218

Gnomad4 OTH AF: 0.0352

Alfa AF: 0.00783 Hom.: 9

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 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142285430; hg19: chr16-2138882;