Variant 18-10794755-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001378183.1(PIEZO2):c.1758+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,467,848 control chromosomes in the GnomAD database, including 1,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 147 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1648 hom. )

Consequence

PIEZO2
NM_001378183.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.140

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=-0.85).

BP6

Variant 18-10794755-G-A is Benign according to our data. Variant chr18-10794755-G-A is described in ClinVar as [Benign]. Clinvar id is 261501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10794755-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0569 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.1758+17C>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.1758+17C>T		intron_variant			NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes

AF:

0.0381

AC:

5795

AN:

152064

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00826

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0601

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0745

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0519

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0366

AC:

4758

AN:

129992

Hom.:

128

AF XY:

0.0360

AC XY:

2503

AN XY:

69438

show subpopulations

Gnomad AFR exome

AF:

0.00761

Gnomad AMR exome

AF:

0.0522

Gnomad ASJ exome

AF:

0.00726

Gnomad EAS exome

AF:

0.00111

Gnomad SAS exome

AF:

0.0155

Gnomad FIN exome

AF:

0.0749

Gnomad NFE exome

AF:

0.0496

Gnomad OTH exome

AF:

0.0283

GnomAD4 exome

AF:

0.0465

AC:

61115

AN:

1315670

Hom.:

1648

Cov.:

AF XY:

0.0455

AC XY:

29626

AN XY:

650996

show subpopulations

Gnomad4 AFR exome

AF:

0.00776

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.00726

Gnomad4 EAS exome

AF:

0.00136

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.0767

Gnomad4 NFE exome

AF:

0.0515

Gnomad4 OTH exome

AF:

0.0417

GnomAD4 genome

AF:

0.0381

AC:

5792

AN:

152178

Hom.:

147

Cov.:

AF XY:

0.0384

AC XY:

2857

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00821

Gnomad4 AMR

AF:

0.0601

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0745

Gnomad4 NFE

AF:

0.0519

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0427

Hom.:

Bravo

AF:

0.0347

Asia WGS

AF:

0.00953

AC:

AN:

3478

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	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 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

-0.85

CADD

Benign

0.25

DANN

Benign

0.43

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