rs6505592

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378183.1(PIEZO2):c.2305C>T(p.Leu769=) 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:7

Conservation

PhyloP100: -1.59

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 261503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10787049-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
PIEZO2	NM_001378183.1 linkuse as main transcript	c.2305C>T	p.Leu769=	synonymous_variant	16/56	ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.2305C>T	p.Leu769=	synonymous_variant	16/56		NM_001378183.1

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

GnomAD3 exomes

AF:

0.860

AC:

121355

AN:

141046

Hom.:

52282

AF XY:

0.861

AC XY:

64476

AN XY:

74898

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 SAS exome

AF:

0.854

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

Gnomad4 AFR exome

AF:

0.801

Gnomad4 AMR exome

AF:

0.863

Gnomad4 ASJ exome

AF:

0.832

Gnomad4 EAS exome

AF:

0.933

Gnomad4 SAS exome

AF:

0.856

Gnomad4 FIN exome

AF:

0.855

Gnomad4 NFE exome

AF:

0.866

Gnomad4 OTH exome

AF:

0.859

GnomAD4 genome

AF:

0.848

AC:

129075

AN:

152132

Hom.:

54824

Cov.:

AF XY:

0.850

AC XY:

63241

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.874

Gnomad4 ASJ

AF:

0.842

Gnomad4 EAS

AF:

0.933

Gnomad4 SAS

AF:

0.857

Gnomad4 FIN

AF:

0.851

Gnomad4 NFE

AF:

0.863

Gnomad4 OTH

AF:

0.845

Alfa

AF:

0.844

Hom.:

9658

Bravo

AF:

0.847

Asia WGS

AF:

0.896

AC:

3109

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Gordon syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Marden-Walker syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis, distal, with impaired proprioception and touch

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.29

DANN

Benign

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over