rs4796901

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378183.1(PIEZO2):c.6031G>C(p.Glu2011Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,536,928 control chromosomes in the GnomAD database, including 42,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3239 hom., cov: 33)

Exomes 𝑓: 0.24 ( 38930 hom. )

Consequence

PIEZO2
NM_001378183.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.53

Publications

15 publications found

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 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

PIEZO2 links:

ENSG00000264843 (HGNC:):

ENSG00000264843 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001565665).

BP6

Variant 18-10704621-C-G is Benign according to our data. Variant chr18-10704621-C-G is described in ClinVar as Benign. ClinVar VariationId is 261519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 link	c.6031G>C	p.Glu2011Gln	missense_variant	Exon 42 of 56	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1 link	c.6031G>C	p.Glu2011Gln	missense_variant	Exon 42 of 56		NM_001378183.1	ENSP00000501957.1		A0A2H4UKA7

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30696

AN:

152072

Hom.:

3237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.225

AC:

31886

AN:

141604

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.230

GnomAD4 exome

AF:

0.235

AC:

325556

AN:

1384738

Hom.:

38930

Cov.:

AF XY:

0.236

AC XY:

161530

AN XY:

683290

show subpopulations

African (AFR)

AF:

0.146

AC:

4597

AN:

31590

American (AMR)

AF:

0.200

AC:

7137

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6142

AN:

25180

East Asian (EAS)

AF:

0.180

AC:

6424

AN:

35732

South Asian (SAS)

AF:

0.279

AC:

22072

AN:

79230

European-Finnish (FIN)

AF:

0.233

AC:

8166

AN:

35000

Middle Eastern (MID)

AF:

0.224

AC:

1274

AN:

5692

European-Non Finnish (NFE)

AF:

0.238

AC:

256691

AN:

1078708

Other (OTH)

AF:

0.225

AC:

13053

AN:

57906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

13887

27775

41662

55550

69437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9012

18024

27036

36048

45060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.202

AC:

30703

AN:

152190

Hom.:

3239

Cov.:

AF XY:

0.202

AC XY:

15045

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.144

AC:

5975

AN:

41540

American (AMR)

AF:

0.189

AC:

2891

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

861

AN:

3470

East Asian (EAS)

AF:

0.180

AC:

932

AN:

5182

South Asian (SAS)

AF:

0.276

AC:

1328

AN:

4814

European-Finnish (FIN)

AF:

0.249

AC:

2640

AN:

10592

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15525

AN:

67984

Other (OTH)

AF:

0.202

AC:

427

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1257

2514

3771

5028

6285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.209

Hom.:

2123

Bravo

AF:

0.198

TwinsUK

AF:

0.242

AC:

897

ALSPAC

AF:

0.241

AC:

929

ESP6500AA

AF:

0.149

AC:

206

ESP6500EA

AF:

0.227

AC:

723

ExAC

AF:

0.219

AC:

4437

Asia WGS

AF:

0.214

AC:

743

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gordon syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Marden-Walker syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arthrogryposis, distal, with impaired proprioception and touch

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.034

.;T;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

M;.;.;M

PhyloP100

7.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;.;.;.

REVEL

Uncertain

0.32

Sift

Benign

0.063

T;.;.;.

Sift4G

Uncertain

0.0060

D;D;D;D

Vest4

0.24

MPC

0.92

ClinPred

0.020

GERP RS

5.4

Varity_R

0.21

gMVP

0.67

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over