rs1395610

chr18-10950760-A-C

Variant summary

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

The NM_001378183.1(PIEZO2):c.286+28775T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,878 control chromosomes in the GnomAD database, including 14,471 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 0.42 (14471 hom., cov: 32)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

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 (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.286+28775T>G		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.286+28775T>G		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64323 AN: 151760 Hom.: 14456 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.424 AC: 64356 AN: 151878 Hom.: 14471 Cov.: 32 AF XY: 0.419 AC XY: 31085 AN XY: 74206

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.457

Alfa AF: 0.489 Hom.: 29955

Bravo AF: 0.419

Asia WGS AF: 0.280 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.3
Dann	Benign	0.65

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: rs1395610; hg19: chr18-10950758;