18-10919332-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.287-8104C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,982 control chromosomes in the GnomAD database, including 6,797 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 0.29 (6797 hom., cov: 33)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.287-8104C>A		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.287-8104C>A		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44700 AN: 151864 Hom.: 6787 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44743 AN: 151982 Hom.: 6797 Cov.: 33 AF XY: 0.291 AC XY: 21602 AN XY: 74290

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.306

Alfa AF: 0.296 Hom.: 9945

Bravo AF: 0.299

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.023
Dann	Benign	0.67

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: rs9964303; hg19: chr18-10919330;