ClinVar Genomic variation as it relates to human health
NM_001142864.4(PIEZO1):c.5289C>G (p.Tyr1763Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001142864.4(PIEZO1):c.5289C>G (p.Tyr1763Ter)
Variation ID: 1163992 Accession: VCV001163992.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q24.3 16: 88721652 (GRCh38) [ NCBI UCSC ] 16: 88788060 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 15, 2021 Feb 14, 2024 Nov 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001142864.4:c.5289C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001136336.2:p.Tyr1763Ter nonsense NC_000016.10:g.88721652G>C NC_000016.9:g.88788060G>C NG_042229.1:g.68569C>G LRG_1137:g.68569C>G LRG_1137t1:c.5289C>G LRG_1137p1:p.Tyr1763Ter - Protein change
- Y1763*
- Other names
- PIEZO1, TYR1763TER (rs72811487)
- Canonical SPDI
- NC_000016.10:88721651:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00031
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PIEZO1 | - | - |
GRCh38 GRCh37 |
1103 | 1779 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 3, 2023 | RCV001509530.9 | |
Pathogenic (1) |
no assertion criteria provided
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Jan 26, 2023 | RCV003152634.1 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 31, 2021 | RCV003147633.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Jul 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001716285.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PVS1, PM2
Number of individuals with the variant: 2
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Likely pathogenic
(May 31, 2021)
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criteria provided, single submitter
Method: clinical testing
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Lymphatic malformation 6
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003834856.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Lymphatic malformation 6
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004048281.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The stop gained p.Y1763* in PIEZO1 (NM_001142864.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The … (more)
The stop gained p.Y1763* in PIEZO1 (NM_001142864.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. The p.Y1763* variant is a loss of function variant in the gene PIEZO1, which is intolerant of Loss of Function variants. The variant has been submitted to ClinVar as Likely Pathogenic.The variant was identified in heterozygous state in one individual in a study where exome sequencing was performed to identify novel variants in unexplained adenomatous polyposis (Spier et al, 2016). For these reasons, this variant has been classified as Likely Pathogenic. The observed variant was also detected in the spouse. (less)
Clinical Features:
Facial asymmetry (present) , Cafe-au-lait spot (present)
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Pathogenic
(Nov 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004169240.1
First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023 |
Comment:
Has not been previously reported as a pathogenic or benign variant in association with PIEZO1-related lymphatic malformation or PIEZO1-related dehydrated hereditary stomatocytosis; however, was observed … (more)
Has not been previously reported as a pathogenic or benign variant in association with PIEZO1-related lymphatic malformation or PIEZO1-related dehydrated hereditary stomatocytosis; however, was observed in an individual with a particular red blood cell antigen described as Er(a-b-) red blood cell phenotype who also possessed a second missense PIEZO variant (Karamatic Crew et al., 2023); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26780541, 34358671, 36122374) (less)
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Pathogenic
(Jul 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002246017.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr1763*) in the PIEZO1 gene. It … (more)
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr1763*) in the PIEZO1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIEZO1 are known to be pathogenic (PMID: 26333996). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with colorectal adenomatous polyposis (PMID: 26780541). ClinVar contains an entry for this variant (Variation ID: 1163992). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. (less)
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Pathogenic
(Jan 26, 2023)
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no assertion criteria provided
Method: literature only
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ER BLOOD GROUP SYSTEM, ER(a-b-)
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV003841039.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment on evidence:
In an woman (P10) with an Er(a-b-) red blood cell phenotype in the Er system (ER; 620207) and anti-Er(3) alloantibodies, Karamatic Crew et al. (2023) … (more)
In an woman (P10) with an Er(a-b-) red blood cell phenotype in the Er system (ER; 620207) and anti-Er(3) alloantibodies, Karamatic Crew et al. (2023) identified compound heterozygous mutations in the PIEZO1 gene: a c.5289C-G transversion (c.5289C-G, NM_001142864.4) in exon 38, resulting in a tyr1763-to-ter (Y1763X) substitution, and E2392K (611184.0018). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were both present in the gnomAD database (frequency of 0.0004 for E2392K and frequency of 0.0001 for Y1763X). Both mutations occurred in the extracellular domain. The E2392K mutation appeared to prevent expression of the Er(a) antigen when carried in cis with wildtype c.7180G (G2394; 611184.0001). The Er(a-b-) phenotype has also been referred to as Er(3-). (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens. | Karamatic Crew V | Blood | 2023 | PMID: 36122374 |
Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis. | Spier I | Familial cancer | 2016 | PMID: 26780541 |
Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. | Fotiou E | Nature communications | 2015 | PMID: 26333996 |
Text-mined citations for rs72811487 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.