rs7234309

Positions:

chr18-10752668-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378183.1(PIEZO2):c.4135G>A(p.Val1379Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,536,748 control chromosomes in the GnomAD database, including 60,652 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7345 hom., cov: 33)

Exomes 𝑓: 0.27 ( 53307 hom. )

Consequence

PIEZO2
NM_001378183.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.84

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.2963705E-4).

BP6

Variant 18-10752668-C-T is Benign according to our data. Variant chr18-10752668-C-T is described in ClinVar as [Benign]. Clinvar id is 261508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10752668-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 linkuse as main transcript	c.4135G>A	p.Val1379Ile	missense_variant	28/56	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.4135G>A	p.Val1379Ile	missense_variant	28/56		NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46037

AN:

151934

Hom.:

7327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.272

AC:

38581

AN:

141626

Hom.:

5827

AF XY:

0.271

AC XY:

20494

AN XY:

75732

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.491

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.274

AC:

378916

AN:

1384696

Hom.:

53307

Cov.:

AF XY:

0.271

AC XY:

185349

AN XY:

683280

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.303

AC:

46077

AN:

152052

Hom.:

7345

Cov.:

AF XY:

0.301

AC XY:

22391

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.284

Hom.:

8014

Bravo

AF:

0.315

TwinsUK

AF:

0.281

AC:

1043

ALSPAC

AF:

0.265

AC:

1021

ESP6500AA

AF:

0.397

AC:

549

ESP6500EA

AF:

0.271

AC:

863

ExAC

AF:

0.245

AC:

4919

Asia WGS

AF:

0.385

AC:

1338

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Gordon syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Marden-Walker syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis, distal, with impaired proprioception and touch

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.025

.;T;.;T

Eigen

Benign

0.097

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

D;D;D;D

MetaRNN

Benign

0.00083

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

L;.;.;L

MutationTaster

Benign

0.043

P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.53

N;.;.;.

REVEL

Benign

0.056

Sift

Benign

0.24

T;.;.;.

Sift4G

Benign

0.14

T;T;T;T

Vest4

0.17

MPC

0.25

ClinPred

0.0068

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over