NM_001378183.1:c.1023G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001378183.1(PIEZO2):c.1023G>A(p.Leu341Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,537,090 control chromosomes in the GnomAD database, including 3,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 292 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3255 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.561

Publications

8 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 18-10807169-C-T is Benign according to our data. Variant chr18-10807169-C-T is described in ClinVar as [Benign]. Clinvar id is 261495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.561 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 link	c.1023G>A	p.Leu341Leu	synonymous_variant	Exon 8 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.1023G>A	p.Leu341Leu	synonymous_variant	Exon 8 of 56		NM_001378183.1	ENSP00000501957.1		A0A2H4UKA7

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8590

AN:

152174

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.0407

Gnomad FIN

AF:

0.0877

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0602

GnomAD2 exomes

AF:

0.0518

AC:

7481

AN:

144440

AF XY:

0.0521

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.0485

Gnomad EAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0648

Gnomad OTH exome

AF:

0.0580

GnomAD4 exome

AF:

0.0661

AC:

91545

AN:

1384798

Hom.:

3255

Cov.:

AF XY:

0.0654

AC XY:

44666

AN XY:

683312

show subpopulations

African (AFR)

AF:

0.0463

AC:

1462

AN:

31592

American (AMR)

AF:

0.0434

AC:

1549

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

1284

AN:

25182

East Asian (EAS)

AF:

0.00109

AC:

AN:

35728

South Asian (SAS)

AF:

0.0438

AC:

3471

AN:

79224

European-Finnish (FIN)

AF:

0.0846

AC:

2963

AN:

35008

Middle Eastern (MID)

AF:

0.0286

AC:

163

AN:

5696

European-Non Finnish (NFE)

AF:

0.0715

AC:

77162

AN:

1078756

Other (OTH)

AF:

0.0596

AC:

3452

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

4376

8751

13127

17502

21878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2962

5924

8886

11848

14810

<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:

0.0564

AC:

8593

AN:

152292

Hom.:

292

Cov.:

AF XY:

0.0568

AC XY:

4231

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0469

AC:

1948

AN:

41560

American (AMR)

AF:

0.0430

AC:

659

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

183

AN:

3472

East Asian (EAS)

AF:

0.00424

AC:

AN:

5184

South Asian (SAS)

AF:

0.0403

AC:

194

AN:

4814

European-Finnish (FIN)

AF:

0.0877

AC:

930

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0664

AC:

4515

AN:

68024

Other (OTH)

AF:

0.0601

AC:

127

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

419

839

1258

1678

2097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0607

Hom.:

104

Bravo

AF:

0.0533

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 09, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.7

(source)

DANN

Benign

0.72

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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