rs1032061

Positions:

• chr18-11013535-G-A

Variant summary

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

The NM_001378183.1(PIEZO2):​c.161-33875C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,206 control chromosomes in the GnomAD database, including 1,583 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 0.13 (1583 hom., cov: 33)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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 = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.161-33875C>T		intron_variant		ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.161-33875C>T		intron_variant			NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19333 AN: 152088 Hom.: 1582 Cov.: 33

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.127 AC: 19337 AN: 152206 Hom.: 1583 Cov.: 33 AF XY: 0.131 AC XY: 9711 AN XY: 74390

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.124

Alfa AF: 0.146 Hom.: 354

Bravo AF: 0.124

Asia WGS AF: 0.134 AC: 466 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	1.3
DANN	Benign	0.64

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: rs1032061; hg19: chr18-11013533;