Variant 18-10797364-T-G 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.1527+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,515,324 control chromosomes in the GnomAD database, including 53,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4601 hom., cov: 31)

Exomes 𝑓: 0.27 ( 49163 hom. )

Consequence

PIEZO2
NM_001378183.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.10

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 18-10797364-T-G is Benign according to our data. Variant chr18-10797364-T-G is described in ClinVar as [Benign]. Clinvar id is 261498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10797364-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 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.1527+10A>C		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1 linkuse as main transcript	c.1527+10A>C		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35219

AN:

151816

Hom.:

4600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.274

AC:

38476

AN:

140654

Hom.:

5529

AF XY:

0.274

AC XY:

20557

AN XY:

75106

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.266

AC:

362035

AN:

1363398

Hom.:

49163

Cov.:

AF XY:

0.266

AC XY:

179154

AN XY:

673786

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.232

AC:

35228

AN:

151926

Hom.:

4601

Cov.:

AF XY:

0.236

AC XY:

17526

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.264

Hom.:

9345

Bravo

AF:

0.225

Asia WGS

AF:

0.289

AC:

1005

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 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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