Variant rs5024299 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001378183.1(PIEZO2):c.4708+18C>T variant causes a intron change. The variant allele was found at a frequency of 0.802 in 1,534,072 control chromosomes in the GnomAD database, including 495,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 53402 hom., cov: 32)

Exomes 𝑓: 0.80 ( 441805 hom. )

Consequence

PIEZO2
NM_001378183.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.11

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 18-10741013-G-A is Benign according to our data. Variant chr18-10741013-G-A is described in ClinVar as [Benign]. Clinvar id is 261510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10741013-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 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.4708+18C>T		intron_variant		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.4708+18C>T		intron_variant			NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126721

AN:

152030

Hom.:

53346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.838

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.763

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.824

GnomAD3 exomes

AF:

0.794

AC:

112605

AN:

141888

Hom.:

45011

AF XY:

0.791

AC XY:

60050

AN XY:

75890

show subpopulations

Gnomad AFR exome

AF:

0.960

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.831

Gnomad EAS exome

AF:

0.907

Gnomad SAS exome

AF:

0.757

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.804

GnomAD4 exome

AF:

0.799

AC:

1103549

AN:

1381924

Hom.:

441805

Cov.:

AF XY:

0.797

AC XY:

543508

AN XY:

682120

show subpopulations

Gnomad4 AFR exome

AF:

0.963

Gnomad4 AMR exome

AF:

0.727

Gnomad4 ASJ exome

AF:

0.829

Gnomad4 EAS exome

AF:

0.898

Gnomad4 SAS exome

AF:

0.762

Gnomad4 FIN exome

AF:

0.753

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.813

GnomAD4 genome

AF:

0.834

AC:

126838

AN:

152148

Hom.:

53402

Cov.:

AF XY:

0.832

AC XY:

61855

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.956

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.838

Gnomad4 EAS

AF:

0.909

Gnomad4 SAS

AF:

0.764

Gnomad4 FIN

AF:

0.765

Gnomad4 NFE

AF:

0.787

Gnomad4 OTH

AF:

0.827

Alfa

AF:

0.812

Hom.:

12599

Bravo

AF:

0.841

Asia WGS

AF:

0.871

AC:

3029

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.26

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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