rs3748421

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001378183.1(PIEZO2):c.7215C>T(p.Ala2405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,610,936 control chromosomes in the GnomAD database, including 88,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6284 hom., cov: 31)

Exomes 𝑓: 0.33 ( 82265 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.584

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 18-10691359-G-A is Benign according to our data. Variant chr18-10691359-G-A is described in ClinVar as [Benign]. Clinvar id is 261526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10691359-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.584 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 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.7215C>T	p.Ala2405=	synonymous_variant	48/56	ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.7215C>T	p.Ala2405=	synonymous_variant	48/56		NM_001378183.1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41579

AN:

151860

Hom.:

6282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.282

AC:

70105

AN:

248420

Hom.:

10932

AF XY:

0.289

AC XY:

38811

AN XY:

134266

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.330

AC:

480888

AN:

1458956

Hom.:

82265

Cov.:

AF XY:

0.329

AC XY:

238437

AN XY:

725722

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.346

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.274

AC:

41589

AN:

151980

Hom.:

6284

Cov.:

AF XY:

0.270

AC XY:

20066

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.315

Hom.:

5582

Bravo

AF:

0.259

Asia WGS

AF:

0.170

AC:

595

AN:

3478

EpiCase

AF:

0.353

EpiControl

AF:

0.343

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	Oct 30, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 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

-0.43

Cadd

Benign

4.0

Dann

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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