16-2088881-G-GCA

Position:

• chr16-2088881-G-GCA

Variant summary

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

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

• Frequency:
  • Genomes: 𝑓 0.045 (274 hom., cov: 0)
  • Exomes 𝑓: 0.042 (209 hom.)
• Consequence: PKD1 NM_001009944.3 3_prime_UTR
• Clinical Significance: Likely 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-GCA is Benign according to our data. Variant chr16-2088881-G-GCA is described in ClinVar as [Likely_benign]. Clinvar id is 1217705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5	c.*288_*289dup		3_prime_UTR_variant	42/42	ENST00000219476.9	NP_000539.2
PKD1	NM_001009944.3	c.*845_*846insTG		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.*288_*289dup		3_prime_UTR_variant	42/42	5	NM_000548.5	ENSP00000219476
PKD1	ENST00000262304.9	c.*845_*846insTG		3_prime_UTR_variant	46/46	1	NM_001009944.3	ENSP00000262304	P5

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6623 AN: 146594 Hom.: 273 Cov.: 0

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0275

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0452

Gnomad NFE AF: 0.0359

Gnomad OTH AF: 0.0519

GnomAD4 exome AF: 0.0421 AC: 11556 AN: 274228 Hom.: 209 Cov.: 0 AF XY: 0.0415 AC XY: 6019 AN XY: 144900

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0334

Gnomad4 FIN exome AF: 0.0239

Gnomad4 NFE exome AF: 0.0301

Gnomad4 OTH exome AF: 0.0406

GnomAD4 genome AF: 0.0452 AC: 6626 AN: 146698 Hom.: 274 Cov.: 0 AF XY: 0.0464 AC XY: 3328 AN XY: 71752

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0275

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.0468

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0359

Gnomad4 OTH AF: 0.0513

Bravo AF: 0.0514

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 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: rs56279647; hg19: chr16-2138882;