rs3748422

Variant summary

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

The NM_001378183.1(PIEZO2):c.7349+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,610,936 control chromosomes in the GnomAD database, including 110,021 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 9846 hom., cov: 31)

Exomes 𝑓: 0.37 ( 100175 hom. )

Consequence

PIEZO2
NM_001378183.1 splice_region, intron

Scores

Splicing: ADA: 0.00008783

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.471

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 (BayesDel_noAF=-0.83).

BP6

Variant 18-10691218-G-A is Benign according to our data. Variant chr18-10691218-G-A is described in ClinVar as [Benign]. Clinvar id is 261527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10691218-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 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.7349+7C>T		splice_region_variant, intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.7349+7C>T		splice_region_variant, intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54617

AN:

151788

Hom.:

9841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.366

GnomAD3 exomes

AF:

0.345

AC:

86175

AN:

249850

Hom.:

15147

AF XY:

0.344

AC XY:

46386

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.352

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.368

AC:

537299

AN:

1459030

Hom.:

100175

Cov.:

AF XY:

0.366

AC XY:

265510

AN XY:

725874

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.354

GnomAD4 genome

AF:

0.360

AC:

54637

AN:

151906

Hom.:

9846

Cov.:

AF XY:

0.357

AC XY:

26465

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.353

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.382

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.370

Hom.:

6350

Bravo

AF:

0.354

Asia WGS

AF:

0.264

AC:

921

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.368

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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

-0.83

Cadd

Benign

3.7

Dann

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0

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