rs2077863

Variant names:

• chr18-11056816-C-G
• rs2077863
• NM_001378183.1:c.160+9311G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

PIEZO2 Gene-Disease associations (from GenCC):

• Gordon syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• arthrogryposis, distal, with impaired proprioception and touch

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics
• arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• connective tissue disorder

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• Marden-Walker syndrome

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.160+9311G>C		intron_variant	Intron 2 of 55	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.160+9311G>C		intron_variant	Intron 2 of 55		NM_001378183.1	ENSP00000501957.1

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

African (AFR) AF: 0.340 AC: 14084 AN: 41408

American (AMR) AF: 0.107 AC: 1635 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3470

East Asian (EAS) AF: 0.0498 AC: 256 AN: 5144

South Asian (SAS) AF: 0.0613 AC: 295 AN: 4816

European-Finnish (FIN) AF: 0.0159 AC: 169 AN: 10606

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0217 AC: 1475 AN: 68018

Other (OTH) AF: 0.104 AC: 220 AN: 2114

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
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2077863; hg19: chr18-11056815;