rs7407105

Variant summary

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

The NM_001378183.1(PIEZO2):c.3867C>T(p.Asn1289=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,536,722 control chromosomes in the GnomAD database, including 491,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 50785 hom., cov: 31)

Exomes 𝑓: 0.80 ( 441099 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

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=-0.46).

BP6

Variant 18-10758025-G-A is Benign according to our data. Variant chr18-10758025-G-A is described in ClinVar as [Benign]. Clinvar id is 261507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10758025-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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.3867C>T	p.Asn1289=	synonymous_variant	27/56	ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.3867C>T	p.Asn1289=	synonymous_variant	27/56		NM_001378183.1

Frequencies

GnomAD3 genomes

AF:

0.815

AC:

123883

AN:

151980

Hom.:

50739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.754

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.788

Gnomad OTH

AF:

0.809

GnomAD3 exomes

AF:

0.791

AC:

114815

AN:

145116

Hom.:

45676

AF XY:

0.790

AC XY:

61063

AN XY:

77260

show subpopulations

Gnomad AFR exome

AF:

0.884

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.839

Gnomad EAS exome

AF:

0.910

Gnomad SAS exome

AF:

0.758

Gnomad FIN exome

AF:

0.775

Gnomad NFE exome

AF:

0.795

Gnomad OTH exome

AF:

0.803

GnomAD4 exome

AF:

0.798

AC:

1104303

AN:

1384624

Hom.:

441099

Cov.:

AF XY:

0.796

AC XY:

544012

AN XY:

683240

show subpopulations

Gnomad4 AFR exome

AF:

0.881

Gnomad4 AMR exome

AF:

0.725

Gnomad4 ASJ exome

AF:

0.837

Gnomad4 EAS exome

AF:

0.900

Gnomad4 SAS exome

AF:

0.762

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.796

Gnomad4 OTH exome

AF:

0.809

GnomAD4 genome

AF:

0.815

AC:

123989

AN:

152098

Hom.:

50785

Cov.:

AF XY:

0.814

AC XY:

60513

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.883

Gnomad4 AMR

AF:

0.753

Gnomad4 ASJ

AF:

0.844

Gnomad4 EAS

AF:

0.911

Gnomad4 SAS

AF:

0.762

Gnomad4 FIN

AF:

0.788

Gnomad4 NFE

AF:

0.788

Gnomad4 OTH

AF:

0.812

Alfa

AF:

0.788

Hom.:

6228

Bravo

AF:

0.817

Asia WGS

AF:

0.867

AC:

3018

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	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

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

-0.46

Cadd

Benign

9.7

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