18-10763009-T-C

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.3036A>G(p.Thr1012Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,537,182 control chromosomes in the GnomAD database, including 496,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52906 hom., cov: 35)

Exomes 𝑓: 0.80 ( 443465 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.382

Publications

19 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=-0.83).

BP6

Variant 18-10763009-T-C is Benign according to our data. Variant chr18-10763009-T-C is described in ClinVar as Benign. ClinVar VariationId is 261504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.382 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 link	c.3036A>G	p.Thr1012Thr	synonymous_variant	Exon 22 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.3036A>G	p.Thr1012Thr	synonymous_variant	Exon 22 of 56		NM_001378183.1	ENSP00000501957.1		A0A2H4UKA7

Frequencies

GnomAD3 genomes

AF:

0.830

AC:

126324

AN:

152176

Hom.:

52852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.933

Gnomad AMI

AF:

0.710

Gnomad AMR

AF:

0.758

Gnomad ASJ

AF:

0.846

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.789

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.789

Gnomad OTH

AF:

0.819

GnomAD2 exomes

AF:

0.795

AC:

114981

AN:

144596

AF XY:

0.794

show subpopulations

Gnomad AFR exome

AF:

0.934

Gnomad AMR exome

AF:

0.721

Gnomad ASJ exome

AF:

0.840

Gnomad EAS exome

AF:

0.914

Gnomad FIN exome

AF:

0.775

Gnomad NFE exome

AF:

0.795

Gnomad OTH exome

AF:

0.806

GnomAD4 exome

AF:

0.799

AC:

1107155

AN:

1384888

Hom.:

443465

Cov.:

AF XY:

0.798

AC XY:

545284

AN XY:

683362

show subpopulations

African (AFR)

AF:

0.935

AC:

29541

AN:

31592

American (AMR)

AF:

0.727

AC:

25962

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

21096

AN:

25180

East Asian (EAS)

AF:

0.902

AC:

32242

AN:

35734

South Asian (SAS)

AF:

0.765

AC:

60601

AN:

79226

European-Finnish (FIN)

AF:

0.776

AC:

27156

AN:

35014

Middle Eastern (MID)

AF:

0.832

AC:

4737

AN:

5696

European-Non Finnish (NFE)

AF:

0.796

AC:

858758

AN:

1078822

Other (OTH)

AF:

0.812

AC:

47062

AN:

57924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

12534

25068

37602

50136

62670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20434

40868

61302

81736

102170

<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:

0.830

AC:

126438

AN:

152294

Hom.:

52906

Cov.:

AF XY:

0.829

AC XY:

61752

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.933

AC:

38787

AN:

41580

American (AMR)

AF:

0.758

AC:

11596

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.846

AC:

2939

AN:

3472

East Asian (EAS)

AF:

0.913

AC:

4733

AN:

5182

South Asian (SAS)

AF:

0.764

AC:

3694

AN:

4832

European-Finnish (FIN)

AF:

0.789

AC:

8349

AN:

10584

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.789

AC:

53703

AN:

68028

Other (OTH)

AF:

0.822

AC:

1739

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1095

2191

3286

4382

5477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.796

Hom.:

15506

Bravo

AF:

0.835

Asia WGS

AF:

0.873

AC:

3038

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

Feb 03, 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

- -

Jul 05, 2018

GeneDx

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

0.36

(source)

DANN

Benign

0.36

PhyloP100

-0.38

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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