rs79992793

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378183.1(PIEZO2):c.6530G>C(p.Arg2177Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00593 in 1,537,244 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 127 hom. )

Consequence

PIEZO2
NM_001378183.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.74

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002460152).

BP6

Variant 18-10699089-C-G is Benign according to our data. Variant chr18-10699089-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 261522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10699089-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO2	NM_001378183.1 linkuse as main transcript	c.6530G>C	p.Arg2177Thr	missense_variant	44/56	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.6530G>C	p.Arg2177Thr	missense_variant	44/56		NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes

AF:

0.00560

AC:

852

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0768

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00962

AC:

1362

AN:

141568

Hom.:

AF XY:

0.00938

AC XY:

710

AN XY:

75708

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.000238

Gnomad EAS exome

AF:

0.0870

Gnomad SAS exome

AF:

0.00299

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.00458

Gnomad OTH exome

AF:

0.00616

GnomAD4 exome

AF:

0.00597

AC:

8267

AN:

1384924

Hom.:

127

Cov.:

AF XY:

0.00583

AC XY:

3982

AN XY:

683388

show subpopulations

Gnomad4 AFR exome

AF:

0.000791

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000159

Gnomad4 EAS exome

AF:

0.0749

Gnomad4 SAS exome

AF:

0.00313

Gnomad4 FIN exome

AF:

0.00297

Gnomad4 NFE exome

AF:

0.00428

Gnomad4 OTH exome

AF:

0.00901

GnomAD4 genome

AF:

0.00558

AC:

850

AN:

152320

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0766

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00625

Hom.:

Bravo

AF:

0.00605

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00283

AC:

ExAC

AF:

0.00384

AC:

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 14, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.019

.;T;.;T

Eigen

Benign

0.089

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;D;D;D

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

M;.;.;M

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

N;.;.;.

REVEL

Uncertain

0.35

Sift

Benign

0.19

T;.;.;.

Sift4G

Benign

0.42

T;T;T;T

Vest4

0.35

MVP

0.32

MPC

0.47

ClinPred

0.021

GERP RS

5.8

Varity_R

0.15

gMVP

0.62

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