Variant chr18-10807169-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001378183.1(PIEZO2):c.1023G>A(p.Leu341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,537,090 control chromosomes in the GnomAD database, including 3,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 292 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3255 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.561

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 18-10807169-C-T is Benign according to our data. Variant chr18-10807169-C-T is described in ClinVar as [Benign]. Clinvar id is 261495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10807169-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.561 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 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.1023G>A	p.Leu341=	synonymous_variant	8/56	ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.1023G>A	p.Leu341=	synonymous_variant	8/56		NM_001378183.1

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8590

AN:

152174

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.0407

Gnomad FIN

AF:

0.0877

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0518

AC:

7481

AN:

144440

Hom.:

229

AF XY:

0.0521

AC XY:

4016

AN XY:

77128

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.0485

Gnomad EAS exome

AF:

0.00216

Gnomad SAS exome

AF:

0.0441

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0648

Gnomad OTH exome

AF:

0.0580

GnomAD4 exome

AF:

0.0661

AC:

91545

AN:

1384798

Hom.:

3255

Cov.:

AF XY:

0.0654

AC XY:

44666

AN XY:

683312

show subpopulations

Gnomad4 AFR exome

AF:

0.0463

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.0510

Gnomad4 EAS exome

AF:

0.00109

Gnomad4 SAS exome

AF:

0.0438

Gnomad4 FIN exome

AF:

0.0846

Gnomad4 NFE exome

AF:

0.0715

Gnomad4 OTH exome

AF:

0.0596

GnomAD4 genome

AF:

0.0564

AC:

8593

AN:

152292

Hom.:

292

Cov.:

AF XY:

0.0568

AC XY:

4231

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0469

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0527

Gnomad4 EAS

AF:

0.00424

Gnomad4 SAS

AF:

0.0403

Gnomad4 FIN

AF:

0.0877

Gnomad4 NFE

AF:

0.0664

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0577

Hom.:

Bravo

AF:

0.0533

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	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

-0.40

CADD

Benign

9.7

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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