rs8086028

Positions:

• chr18-10737781-G-A
• chr18-10737781-G-C
• chr18-10737781-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378183.1(PIEZO2):​c.4709-1071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,024 control chromosomes in the GnomAD database, including 11,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11224 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

Genes affected

PIEZO2 (HGNC:26270): (piezo type mechanosensitive ion channel component 2) The protein encoded by this gene contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels. These channels serve to connect mechanical forces to biological signals. The encoded protein quickly adapts MA currents in somatosensory neurons. Defects in this gene are a cause of type 5 distal arthrogryposis. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.4709-1071C>T		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.4709-1071C>T		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54613 AN: 151906 Hom.: 11204 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.354

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.360 AC: 54665 AN: 152024 Hom.: 11224 Cov.: 33 AF XY: 0.357 AC XY: 26517 AN XY: 74290

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.362

Alfa AF: 0.283 Hom.: 13224

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.62

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: rs8086028; hg19: chr18-10737779;