Variant rs2290902 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142864.4(PIEZO1):c.7059T>C(p.Pro2353Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,491,590 control chromosomes in the GnomAD database, including 593,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59024 hom., cov: 34)

Exomes 𝑓: 0.89 ( 534628 hom. )

Consequence

PIEZO1
NM_001142864.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.343

Variant links:

Genes affected

PIEZO1 (HGNC:28993): (piezo type mechanosensitive ion channel component 1 (Er blood group)) The protein encoded by this gene is a mechanically-activated ion channel that links mechanical forces to biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer. Defects in this gene have been associated with dehydrated hereditary stomatocytosis. [provided by RefSeq, Jul 2015]

PIEZO1 links:

PIEZO1 (HGNC:):

PIEZO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-88716268-A-G is Benign according to our data. Variant chr16-88716268-A-G is described in ClinVar as [Benign]. Clinvar id is 440040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88716268-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.343 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO1	NM_001142864.4 linkuse as main transcript	c.7059T>C	p.Pro2353Pro	synonymous_variant	49/51	ENST00000301015.14	NP_001136336.2	Q92508
MIR4722	NR_039873.1 linkuse as main transcript	n.*10T>C		downstream_gene_variant
MIR4722	unassigned_transcript_2912 use as main transcript	n.*10T>C		downstream_gene_variant
MIR4722	unassigned_transcript_2913 use as main transcript	n.*47T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14 linkuse as main transcript	c.7059T>C	p.Pro2353Pro	synonymous_variant	49/51	1	NM_001142864.4	ENSP00000301015.9		Q92508

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133868

AN:

152152

Hom.:

58996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.944

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.864

Gnomad FIN

AF:

0.852

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.904

Gnomad OTH

AF:

0.889

GnomAD3 exomes

AF:

0.883

AC:

97080

AN:

109958

Hom.:

42871

AF XY:

0.883

AC XY:

49151

AN XY:

55658

show subpopulations

Gnomad AFR exome

AF:

0.836

Gnomad AMR exome

AF:

0.862

Gnomad ASJ exome

AF:

0.951

Gnomad EAS exome

AF:

0.882

Gnomad SAS exome

AF:

0.855

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.907

Gnomad OTH exome

AF:

0.904

GnomAD4 exome

AF:

0.893

AC:

1196461

AN:

1339320

Hom.:

534628

Cov.:

AF XY:

0.893

AC XY:

583357

AN XY:

652920

show subpopulations

Gnomad4 AFR exome

AF:

0.839

Gnomad4 AMR exome

AF:

0.860

Gnomad4 ASJ exome

AF:

0.949

Gnomad4 EAS exome

AF:

0.892

Gnomad4 SAS exome

AF:

0.863

Gnomad4 FIN exome

AF:

0.871

Gnomad4 NFE exome

AF:

0.898

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.880

AC:

133952

AN:

152270

Hom.:

59024

Cov.:

AF XY:

0.876

AC XY:

65239

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.840

Gnomad4 AMR

AF:

0.874

Gnomad4 ASJ

AF:

0.950

Gnomad4 EAS

AF:

0.894

Gnomad4 SAS

AF:

0.864

Gnomad4 FIN

AF:

0.852

Gnomad4 NFE

AF:

0.904

Gnomad4 OTH

AF:

0.888

Alfa

AF:

0.899

Hom.:

45814

Bravo

AF:

0.878

Asia WGS

AF:

0.864

AC:

3005

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Lymphatic malformation 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

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

-0.94

CADD

Benign

2.4

DANN

Benign

0.36

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