rs11663246

chr18-10900616-G-Achr18-10900616-G-Cchr18-10900616-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.329+10570C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,988 control chromosomes in the GnomAD database, including 8,422 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 0.33 (8422 hom., cov: 32)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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]

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.329+10570C>T		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.329+10570C>T		intron_variant			NM_001378183.1
	ENST00000584321.1	n.58+6942G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50340 AN: 151870 Hom.: 8403 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.332 AC: 50398 AN: 151988 Hom.: 8422 Cov.: 32 AF XY: 0.327 AC XY: 24299 AN XY: 74286

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.349

Alfa AF: 0.321 Hom.: 9243

Bravo AF: 0.332

Asia WGS AF: 0.290 AC: 1010 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	1.0
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: rs11663246; hg19: chr18-10900614;