chr18-10696229-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378183.1(PIEZO2):c.7035G>A(p.Pro2345Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,820 control chromosomes in the GnomAD database, including 90,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6938 hom., cov: 33)

Exomes 𝑓: 0.33 ( 83257 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.33

Publications

18 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 18-10696229-C-T is Benign according to our data. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10696229-C-T is described in CliVar as Benign. Clinvar id is 261525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 link	c.7035G>A	p.Pro2345Pro	synonymous_variant	Exon 47 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.7035G>A	p.Pro2345Pro	synonymous_variant	Exon 47 of 56		NM_001378183.1	ENSP00000501957.1		A0A2H4UKA7

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44728

AN:

152038

Hom.:

6932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.307

GnomAD2 exomes

AF:

0.287

AC:

72187

AN:

251218

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.332

AC:

485518

AN:

1461664

Hom.:

83257

Cov.:

AF XY:

0.331

AC XY:

240521

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.225

AC:

7539

AN:

33476

American (AMR)

AF:

0.189

AC:

8475

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

9167

AN:

26136

East Asian (EAS)

AF:

0.139

AC:

5522

AN:

39700

South Asian (SAS)

AF:

0.256

AC:

22061

AN:

86252

European-Finnish (FIN)

AF:

0.322

AC:

17187

AN:

53418

Middle Eastern (MID)

AF:

0.286

AC:

1651

AN:

5768

European-Non Finnish (NFE)

AF:

0.355

AC:

394918

AN:

1111806

Other (OTH)

AF:

0.315

AC:

18998

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

20102

40204

60305

80407

100509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12332

24664

36996

49328

61660

<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:

0.294

AC:

44747

AN:

152156

Hom.:

6938

Cov.:

AF XY:

0.290

AC XY:

21548

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.227

AC:

9426

AN:

41516

American (AMR)

AF:

0.249

AC:

3805

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

1262

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

563

AN:

5172

South Asian (SAS)

AF:

0.234

AC:

1131

AN:

4824

European-Finnish (FIN)

AF:

0.323

AC:

3421

AN:

10578

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24123

AN:

67994

Other (OTH)

AF:

0.304

AC:

640

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1615

3231

4846

6462

8077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.324

Hom.:

23486

Bravo

AF:

0.282

Asia WGS

AF:

0.177

AC:

619

AN:

3478

EpiCase

AF:

0.356

EpiControl

AF:

0.345

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 16, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.18

(source)

DANN

Benign

0.56

PhyloP100

-3.3

Mutation Taster

=82/18

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

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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