rs12455924

Variant names:

• chr18-11064410-C-T
• rs12455924
• NM_001378183.1:c.160+1717G>A

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+1717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,154 control chromosomes in the GnomAD database, including 2,679 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 0.15 (2679 hom., cov: 32)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.160+1717G>A		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+1717G>A		intron_variant	Intron 2 of 55		NM_001378183.1	ENSP00000501957.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23003 AN: 152036 Hom.: 2672 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00924

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.151 AC: 23049 AN: 152154 Hom.: 2679 Cov.: 32 AF XY: 0.148 AC XY: 11033 AN XY: 74416

African (AFR) AF: 0.328 AC: 13609 AN: 41470

American (AMR) AF: 0.105 AC: 1599 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3468

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5180

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4822

European-Finnish (FIN) AF: 0.0524 AC: 556 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6224 AN: 68004

Other (OTH) AF: 0.134 AC: 283 AN: 2114

Alfa AF: 0.106 Hom.: 1302

Bravo AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.027
DANN	Benign	0.43
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12455924; hg19: chr18-11064409;