Variant rs73945841 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.6600C>T(p.Phe2200Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,537,110 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 96 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 96 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.34

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:

PIEZO2 (HGNC:):

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=-0.43).

BP6

Variant 18-10699019-G-A is Benign according to our data. Variant chr18-10699019-G-A is described in ClinVar as [Benign]. Clinvar id is 261523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.067 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.6600C>T	p.Phe2200Phe	synonymous_variant	44/56	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.6600C>T	p.Phe2200Phe	synonymous_variant	44/56		NM_001378183.1	ENSP00000501957.1		A0A2H4UKA7

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3126

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0692

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00994

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00560

AC:

793

AN:

141610

Hom.:

AF XY:

0.00465

AC XY:

352

AN XY:

75754

show subpopulations

Gnomad AFR exome

AF:

0.0723

Gnomad AMR exome

AF:

0.00558

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00247

AC:

3416

AN:

1384798

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1545

AN XY:

683346

show subpopulations

Gnomad4 AFR exome

AF:

0.0749

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.00798

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.000189

Gnomad4 FIN exome

AF:

0.0000287

Gnomad4 NFE exome

AF:

0.000254

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.0206

AC:

3133

AN:

152312

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1455

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0691

Gnomad4 AMR

AF:

0.00993

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.0226

Asia WGS

AF:

0.00491

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

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

-0.43

CADD

Benign

7.4

DANN

Benign

0.71

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