18-10748605-A-T

Variant summary

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

The NM_001378183.1(PIEZO2):c.4290T>A(p.Leu1430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,524,030 control chromosomes in the GnomAD database, including 242,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 32696 hom., cov: 32)

Exomes 𝑓: 0.55 ( 209711 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.27

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=-0.85).

BP6

Variant 18-10748605-A-T is Benign according to our data. Variant chr18-10748605-A-T is described in ClinVar as [Benign]. Clinvar id is 261509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10748605-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 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.4290T>A	p.Leu1430=	synonymous_variant	30/56	ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.4290T>A	p.Leu1430=	synonymous_variant	30/56		NM_001378183.1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96295

AN:

151974

Hom.:

32645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.603

GnomAD3 exomes

AF:

0.548

AC:

71089

AN:

129772

Hom.:

20354

AF XY:

0.544

AC XY:

37629

AN XY:

69170

show subpopulations

Gnomad AFR exome

AF:

0.902

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.706

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.555

Gnomad OTH exome

AF:

0.548

GnomAD4 exome

AF:

0.548

AC:

751889

AN:

1371940

Hom.:

209711

Cov.:

AF XY:

0.544

AC XY:

368256

AN XY:

676414

show subpopulations

Gnomad4 AFR exome

AF:

0.906

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.662

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.634

AC:

96391

AN:

152090

Hom.:

32696

Cov.:

AF XY:

0.628

AC XY:

46688

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.891

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.695

Gnomad4 SAS

AF:

0.476

Gnomad4 FIN

AF:

0.488

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.608

Alfa

AF:

0.509

Hom.:

2786

Bravo

AF:

0.648

Asia WGS

AF:

0.655

AC:

2280

AN:

3478

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

-0.85

Cadd

Benign

1.3

Dann

Benign

0.57

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