Variant rs76488076 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001378183.1(PIEZO2):c.2226T>C(p.Ile742=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 1,535,012 control chromosomes in the GnomAD database, including 3,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 286 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3193 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00600

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 18-10787128-A-G is Benign according to our data. Variant chr18-10787128-A-G is described in ClinVar as [Benign]. Clinvar id is 261502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10787128-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.006 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0642 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.2226T>C	p.Ile742=	synonymous_variant	16/56	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.2226T>C	p.Ile742=	synonymous_variant	16/56		NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8391

AN:

152136

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0435

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0429

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.0395

Gnomad FIN

AF:

0.0869

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0595

GnomAD3 exomes

AF:

0.0499

AC:

7159

AN:

143490

Hom.:

219

AF XY:

0.0502

AC XY:

3840

AN XY:

76534

show subpopulations

Gnomad AFR exome

AF:

0.0437

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.00217

Gnomad SAS exome

AF:

0.0422

Gnomad FIN exome

AF:

0.0853

Gnomad NFE exome

AF:

0.0633

Gnomad OTH exome

AF:

0.0554

GnomAD4 exome

AF:

0.0653

AC:

90341

AN:

1382758

Hom.:

3193

Cov.:

AF XY:

0.0646

AC XY:

44082

AN XY:

682276

show subpopulations

Gnomad4 AFR exome

AF:

0.0432

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.00109

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.0842

Gnomad4 NFE exome

AF:

0.0708

Gnomad4 OTH exome

AF:

0.0591

GnomAD4 genome

AF:

0.0551

AC:

8395

AN:

152254

Hom.:

286

Cov.:

AF XY:

0.0554

AC XY:

4121

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.0428

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.00462

Gnomad4 SAS

AF:

0.0391

Gnomad4 FIN

AF:

0.0869

Gnomad4 NFE

AF:

0.0659

Gnomad4 OTH

AF:

0.0594

Alfa

AF:

0.0553

Hom.:

Bravo

AF:

0.0523

Asia WGS

AF:

0.0240

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.0

DANN

Benign

0.77

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