rs6505592

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.2305C>T(p.Leu769Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,529,326 control chromosomes in the GnomAD database, including 570,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 54824 hom., cov: 31)

Exomes 𝑓: 0.86 ( 515351 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.59

Publications

16 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=-0.84).

BP6

Variant 18-10787049-G-A is Benign according to our data. Variant chr18-10787049-G-A is described in ClinVar as Benign. ClinVar VariationId is 261503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 link	c.2305C>T	p.Leu769Leu	synonymous_variant	Exon 16 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.2305C>T	p.Leu769Leu	synonymous_variant	Exon 16 of 56		NM_001378183.1	ENSP00000501957.1		A0A2H4UKA7

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128972

AN:

152014

Hom.:

54779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.804

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.874

Gnomad ASJ

AF:

0.842

Gnomad EAS

AF:

0.933

Gnomad SAS

AF:

0.856

Gnomad FIN

AF:

0.851

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.844

GnomAD2 exomes

AF:

0.860

AC:

121355

AN:

141046

AF XY:

0.861

show subpopulations

Gnomad AFR exome

AF:

0.792

Gnomad AMR exome

AF:

0.859

Gnomad ASJ exome

AF:

0.831

Gnomad EAS exome

AF:

0.932

Gnomad FIN exome

AF:

0.856

Gnomad NFE exome

AF:

0.865

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.865

AC:

1190866

AN:

1377194

Hom.:

515351

Cov.:

AF XY:

0.864

AC XY:

587476

AN XY:

679578

show subpopulations

African (AFR)

AF:

0.801

AC:

24969

AN:

31172

American (AMR)

AF:

0.863

AC:

29533

AN:

34204

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

20816

AN:

25034

East Asian (EAS)

AF:

0.933

AC:

33272

AN:

35646

South Asian (SAS)

AF:

0.856

AC:

66597

AN:

77832

European-Finnish (FIN)

AF:

0.855

AC:

30006

AN:

35086

Middle Eastern (MID)

AF:

0.844

AC:

4749

AN:

5624

European-Non Finnish (NFE)

AF:

0.866

AC:

931331

AN:

1074890

Other (OTH)

AF:

0.859

AC:

49593

AN:

57706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

8095

16189

24284

32378

40473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20822

41644

62466

83288

104110

<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:

0.848

AC:

129075

AN:

152132

Hom.:

54824

Cov.:

AF XY:

0.850

AC XY:

63241

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.805

AC:

33364

AN:

41468

American (AMR)

AF:

0.874

AC:

13358

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.842

AC:

2925

AN:

3472

East Asian (EAS)

AF:

0.933

AC:

4823

AN:

5170

South Asian (SAS)

AF:

0.857

AC:

4132

AN:

4824

European-Finnish (FIN)

AF:

0.851

AC:

9012

AN:

10588

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.863

AC:

58667

AN:

68008

Other (OTH)

AF:

0.845

AC:

1787

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1007

2014

3020

4027

5034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.846

Hom.:

17529

Bravo

AF:

0.847

Asia WGS

AF:

0.896

AC:

3109

AN:

3470

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

- -

Jul 05, 2018

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

-0.84

CADD

Benign

0.29

(source)

DANN

Benign

0.43

PhyloP100

-1.6

Mutation Taster

=98/2

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