This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.349C>T (p.Gln117Ter)
Germline
Classification
Help
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.
(2)
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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.
Pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004329.3(BMPR1A):c.349C>T (p.Gln117Ter)
Variation ID: 2584273 Accession: VCV002584273.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86899809 (GRCh38) [ NCBI UCSC ] 10: 88659566 (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 Oct 21, 2023 Aug 11, 2024 Apr 3, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004329.3:c.349C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Gln117Ter nonsense NM_001406559.1:c.349C>T NP_001393488.1:p.Gln117Ter nonsense NM_001406560.1:c.349C>T NP_001393489.1:p.Gln117Ter nonsense NM_001406561.1:c.349C>T NP_001393490.1:p.Gln117Ter nonsense NM_001406562.1:c.349C>T NP_001393491.1:p.Gln117Ter nonsense NM_001406563.1:c.349C>T NP_001393492.1:p.Gln117Ter nonsense NM_001406564.1:c.349C>T NP_001393493.1:p.Gln117Ter nonsense NM_001406565.1:c.349C>T NP_001393494.1:p.Gln117Ter nonsense NM_001406566.1:c.349C>T NP_001393495.1:p.Gln117Ter nonsense NM_001406567.1:c.349C>T NP_001393496.1:p.Gln117Ter nonsense NM_001406568.1:c.349C>T NP_001393497.1:p.Gln117Ter nonsense NM_001406569.1:c.349C>T NP_001393498.1:p.Gln117Ter nonsense NM_001406570.1:c.349C>T NP_001393499.1:p.Gln117Ter nonsense NM_001406571.1:c.349C>T NP_001393500.1:p.Gln117Ter nonsense NM_001406572.1:c.349C>T NP_001393501.1:p.Gln117Ter nonsense NM_001406573.1:c.349C>T NP_001393502.1:p.Gln117Ter nonsense NM_001406574.1:c.349C>T NP_001393503.1:p.Gln117Ter nonsense NM_001406575.1:c.349C>T NP_001393504.1:p.Gln117Ter nonsense NM_001406576.1:c.349C>T NP_001393505.1:p.Gln117Ter nonsense NM_001406577.1:c.349C>T NP_001393506.1:p.Gln117Ter nonsense NM_001406578.1:c.349C>T NP_001393507.1:p.Gln117Ter nonsense NM_001406579.1:c.349C>T NP_001393508.1:p.Gln117Ter nonsense NM_001406580.1:c.349C>T NP_001393509.1:p.Gln117Ter nonsense NM_001406581.1:c.349C>T NP_001393510.1:p.Gln117Ter nonsense NM_001406582.1:c.349C>T NP_001393511.1:p.Gln117Ter nonsense NM_001406583.1:c.349C>T NP_001393512.1:p.Gln117Ter nonsense NM_001406584.1:c.265C>T NP_001393513.1:p.Gln89Ter nonsense NM_001406585.1:c.265C>T NP_001393514.1:p.Gln89Ter nonsense NM_001406586.1:c.265C>T NP_001393515.1:p.Gln89Ter nonsense NM_001406587.1:c.265C>T NP_001393516.1:p.Gln89Ter nonsense NM_001406588.1:c.265C>T NP_001393517.1:p.Gln89Ter nonsense NM_001406589.1:c.333+7580C>T intron variant NR_176211.1:n.917C>T non-coding transcript variant NR_176212.1:n.917C>T non-coding transcript variant NR_176213.1:n.917C>T non-coding transcript variant NC_000010.11:g.86899809C>T NC_000010.10:g.88659566C>T NG_009362.1:g.148171C>T LRG_298:g.148171C>T LRG_298t1:c.349C>T LRG_298p1:p.Gln117Ter - Protein change
- Q117*, Q89*
- Other names
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- Canonical SPDI
- NC_000010.11:86899808:C:T
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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.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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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| BMPR1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2329 | 2425 | |
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
Help
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 (1) |
criteria provided, single submitter
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May 26, 2023 | RCV003335721.2 | |
| Pathogenic (1) |
criteria provided, single submitter
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Apr 3, 2024 | RCV004604940.1 |
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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Pathogenic
(May 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004044977.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Apr 03, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005095231.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
The p.Q117* pathogenic mutation (also known as c.349C>T), located in coding exon 4 of the BMPR1A gene, results from a C to T substitution at … (more)
The p.Q117* pathogenic mutation (also known as c.349C>T), located in coding exon 4 of the BMPR1A gene, results from a C to T substitution at nucleotide position 349. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This variant has been detected in patients with juvenile polyposis syndrome (JPS) (Sayed MG et al. Ann Surg Oncol, 2002 Nov;9:901-6; Aretz S et al. J Med Genet, 2007 Nov;44:702-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Comment:
Comment:
The p.Q117* pathogenic mutation (also known as c.349C>T), located in coding exon 4 of the BMPR1A gene, results from a C to T substitution at nucleotide position 349. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This variant has been detected in patients with juvenile polyposis syndrome (JPS) (Sayed MG et al. Ann Surg Oncol, 2002 Nov;9:901-6; Aretz S et al. J Med Genet, 2007 Nov;44:702-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
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. |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Comment:
The p.Q117* pathogenic mutation (also known as c.349C>T), located in coding exon 4 of the BMPR1A gene, results from a C to T substitution at nucleotide position 349. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This variant has been detected in patients with juvenile polyposis syndrome (JPS) (Sayed MG et al. Ann Surg Oncol, 2002 Nov;9:901-6; Aretz S et al. J Med Genet, 2007 Nov;44:702-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. | Aretz S | Journal of medical genetics | 2007 | PMID: 17873119 |
| Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. | Sayed MG | Annals of surgical oncology | 2002 | PMID: 12417513 |
Text-mined citations for this variant ...
HelpRecord last updated Aug 11, 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.