rs7227022

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5589C>T(p.Ser1863Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,515,782 control chromosomes in the GnomAD database, including 59,509 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5698 hom., cov: 32)

Exomes 𝑓: 0.28 ( 53811 hom. )

Consequence

PIEZO2
NM_001378183.1 splice_region, synonymous

Scores

Splicing: ADA: 0.00002552

Clinical Significance

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

Conservation

PhyloP100: -0.236

Publications

13 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 18-10705746-G-A is Benign according to our data. Variant chr18-10705746-G-A is described in ClinVar as Benign. ClinVar VariationId is 261514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.236 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 link	c.5589C>T	p.Ser1863Ser	splice_region_variant, synonymous_variant	Exon 41 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.5589C>T	p.Ser1863Ser	splice_region_variant, synonymous_variant	Exon 41 of 56		NM_001378183.1	ENSP00000501957.1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41010

AN:

151900

Hom.:

5696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.309

AC:

38315

AN:

124062

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.278

AC:

378634

AN:

1363764

Hom.:

53811

Cov.:

AF XY:

0.278

AC XY:

186301

AN XY:

670294

show subpopulations

African (AFR)

AF:

0.238

AC:

7371

AN:

30994

American (AMR)

AF:

0.396

AC:

13287

AN:

33570

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

6524

AN:

23902

East Asian (EAS)

AF:

0.439

AC:

15557

AN:

35456

South Asian (SAS)

AF:

0.301

AC:

23272

AN:

77392

European-Finnish (FIN)

AF:

0.272

AC:

9203

AN:

33798

Middle Eastern (MID)

AF:

0.261

AC:

1445

AN:

5542

European-Non Finnish (NFE)

AF:

0.269

AC:

286609

AN:

1066280

Other (OTH)

AF:

0.270

AC:

15366

AN:

56830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

14029

28058

42086

56115

70144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10076

20152

30228

40304

50380

<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:

0.270

AC:

41025

AN:

152018

Hom.:

5698

Cov.:

AF XY:

0.273

AC XY:

20290

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.238

AC:

9887

AN:

41490

American (AMR)

AF:

0.338

AC:

5161

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

966

AN:

3468

East Asian (EAS)

AF:

0.396

AC:

2039

AN:

5152

South Asian (SAS)

AF:

0.300

AC:

1441

AN:

4804

European-Finnish (FIN)

AF:

0.288

AC:

3042

AN:

10554

Middle Eastern (MID)

AF:

0.233

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.262

AC:

17806

AN:

67950

Other (OTH)

AF:

0.259

AC:

546

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1512

3024

4535

6047

7559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.262

Hom.:

13363

Bravo

AF:

0.275

Asia WGS

AF:

0.306

AC:

1064

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.032

(source)

DANN

Benign

0.84

PhyloP100

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=75/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.020

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