The c.24_31delCAGATTAT variant, located in coding exon 1 of the BMPR1A gene, results from a deletion of 8 nucleotides at nucleotide positions 24 to 31, causing a translational frameshift with a predicted alternate stop codon (p.R9Gfs*17). The predicted stop codon occurs in the 5’ end of theBMPR1A gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant has been observed in at least one individual with a personal and/or family history that is consistent with BMPR1A-related juvenile polyposis syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.24_31del (p.Arg9fs)
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.
(1)
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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.
Likely pathogenic
1
criteria provided, single submitter
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.24_31del (p.Arg9fs)
Variation ID: 3223950 Accession: VCV003223950.1
- Type and length
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Deletion, 8 bp
- Location
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Cytogenetic: 10q23.2 10: 86876040-86876047 (GRCh38) [ NCBI UCSC ] 10: 88635797-88635804 (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 May 1, 2024 May 1, 2024 Feb 27, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004329.3:c.24_31del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Arg9fs frameshift NM_001406559.1:c.24_31del NP_001393488.1:p.Arg9fs frameshift NM_001406560.1:c.24_31del NP_001393489.1:p.Arg9fs frameshift NM_001406561.1:c.24_31del NP_001393490.1:p.Arg9fs frameshift NM_001406562.1:c.24_31del NP_001393491.1:p.Arg9fs frameshift NM_001406563.1:c.24_31del NP_001393492.1:p.Arg9fs frameshift NM_001406564.1:c.24_31del NP_001393493.1:p.Arg9fs frameshift NM_001406565.1:c.24_31del NP_001393494.1:p.Arg9fs frameshift NM_001406566.1:c.24_31del NP_001393495.1:p.Arg9fs frameshift NM_001406567.1:c.24_31del NP_001393496.1:p.Arg9fs frameshift NM_001406568.1:c.24_31del NP_001393497.1:p.Arg9fs frameshift NM_001406569.1:c.24_31del NP_001393498.1:p.Arg9fs frameshift NM_001406570.1:c.24_31del NP_001393499.1:p.Arg9fs frameshift NM_001406571.1:c.24_31del NP_001393500.1:p.Arg9fs frameshift NM_001406572.1:c.24_31del NP_001393501.1:p.Arg9fs frameshift NM_001406573.1:c.24_31del NP_001393502.1:p.Arg9fs frameshift NM_001406574.1:c.24_31del NP_001393503.1:p.Arg9fs frameshift NM_001406575.1:c.24_31del NP_001393504.1:p.Arg9fs frameshift NM_001406576.1:c.24_31del NP_001393505.1:p.Arg9fs frameshift NM_001406577.1:c.24_31del NP_001393506.1:p.Arg9fs frameshift NM_001406578.1:c.24_31del NP_001393507.1:p.Arg9fs frameshift NM_001406579.1:c.24_31del NP_001393508.1:p.Arg9fs frameshift NM_001406580.1:c.24_31del NP_001393509.1:p.Arg9fs frameshift NM_001406581.1:c.24_31del NP_001393510.1:p.Arg9fs frameshift NM_001406582.1:c.24_31del NP_001393511.1:p.Arg9fs frameshift NM_001406583.1:c.24_31del NP_001393512.1:p.Arg9fs frameshift NM_001406584.1:c.-17-14020_-17-14013del intron variant NM_001406585.1:c.-17-14020_-17-14013del intron variant NM_001406586.1:c.-12-14025_-12-14018del intron variant NM_001406587.1:c.-17-14020_-17-14013del intron variant NM_001406588.1:c.-56_-49del 5 prime UTR NM_001406589.1:c.24_31del NP_001393518.1:p.Arg9fs frameshift NR_176211.1:n.592_599del non-coding transcript variant NR_176212.1:n.592_599del non-coding transcript variant NR_176213.1:n.592_599del non-coding transcript variant NC_000010.11:g.86876042_86876049del NC_000010.10:g.88635799_88635806del NG_009362.1:g.124404_124411del LRG_298:g.124404_124411del LRG_298t1:c.24_31del LRG_298p1:p.Arg9Glyfs - Protein change
- R9fs
- Other names
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- Canonical SPDI
- NC_000010.11:86876039:ATCAGATTAT:AT
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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 |
2441 | 2537 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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Feb 27, 2024 | RCV004516714.1 |
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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Likely pathogenic
(Feb 27, 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: SCV005022025.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.24_31delCAGATTAT variant, located in coding exon 1 of the BMPR1A gene, results from a deletion of 8 nucleotides at nucleotide positions 24 to 31, … (more)
The c.24_31delCAGATTAT variant, located in coding exon 1 of the BMPR1A gene, results from a deletion of 8 nucleotides at nucleotide positions 24 to 31, causing a translational frameshift with a predicted alternate stop codon (p.R9Gfs*17). The predicted stop codon occurs in the 5’ end of theBMPR1A gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant has been observed in at least one individual with a personal and/or family history that is consistent with BMPR1A-related juvenile polyposis syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
|
Comment:
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:
The c.24_31delCAGATTAT variant, located in coding exon 1 of the BMPR1A gene, results from a deletion of 8 nucleotides at nucleotide positions 24 to 31, causing a translational frameshift with a predicted alternate stop codon (p.R9Gfs*17). The predicted stop codon occurs in the 5’ end of theBMPR1A gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant has been observed in at least one individual with a personal and/or family history that is consistent with BMPR1A-related juvenile polyposis syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 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.