rs2077863

chr18-11056816-C-G

Variant summary

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

The NM_001378183.1(PIEZO2):c.160+9311G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,060 control chromosomes in the GnomAD database, including 2,529 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 0.12 (2529 hom., cov: 32)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.160+9311G>C		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.160+9311G>C		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18396 AN: 151942 Hom.: 2518 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.121 AC: 18456 AN: 152060 Hom.: 2529 Cov.: 32 AF XY: 0.119 AC XY: 8881 AN XY: 74346

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.0498

Gnomad4 SAS AF: 0.0613

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0789 Hom.: 184

Bravo AF: 0.138

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.66
Dann	Benign	0.47

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: rs2077863; hg19: chr18-11056815;