chr16-2088881-G-GCGCACA

Position:

• chr16-2088881-G-GCGCACA

Variant summary

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

The NM_001009944.3(PKD1):​c.*845_*846insTGTGCG 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 0.14 (2343 hom., cov: 0)
  • Exomes 𝑓: 0.048 (287 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-GCGCACA is Benign according to our data. Variant chr16-2088881-G-GCGCACA is described in ClinVar as [Benign]. Clinvar id is 1229544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.142 AC: 20739 AN: 146246 Hom.: 2341 Cov.: 0

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0484 AC: 13239 AN: 273490 Hom.: 287 Cov.: 0 AF XY: 0.0456 AC XY: 6599 AN XY: 144600

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.0511

Gnomad4 ASJ exome AF: 0.0829

Gnomad4 EAS exome AF: 0.0000534

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.0390

Gnomad4 NFE exome AF: 0.0507

Gnomad4 OTH exome AF: 0.0634

GnomAD4 genome AF: 0.142 AC: 20765 AN: 146350 Hom.: 2343 Cov.: 0 AF XY: 0.137 AC XY: 9814 AN XY: 71578

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.000587

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0258 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 20, 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;