This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 1750242). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 196 of the BMPR1A protein (p.Asp196Val).
ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.587A>T (p.Asp196Val)
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)
Help
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.
Uncertain significance
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.587A>T (p.Asp196Val)
Variation ID: 1750242 Accession: VCV001750242.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86912296 (GRCh38) [ NCBI UCSC ] 10: 88672053 (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 Nov 29, 2022 May 1, 2024 Sep 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004329.3:c.587A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Asp196Val missense NM_001406559.1:c.662A>T NP_001393488.1:p.Asp221Val missense NM_001406560.1:c.635A>T NP_001393489.1:p.Asp212Val missense NM_001406561.1:c.587A>T NP_001393490.1:p.Asp196Val missense NM_001406562.1:c.587A>T NP_001393491.1:p.Asp196Val missense NM_001406563.1:c.587A>T NP_001393492.1:p.Asp196Val missense NM_001406564.1:c.587A>T NP_001393493.1:p.Asp196Val missense NM_001406565.1:c.587A>T NP_001393494.1:p.Asp196Val missense NM_001406566.1:c.587A>T NP_001393495.1:p.Asp196Val missense NM_001406567.1:c.587A>T NP_001393496.1:p.Asp196Val missense NM_001406568.1:c.587A>T NP_001393497.1:p.Asp196Val missense NM_001406569.1:c.587A>T NP_001393498.1:p.Asp196Val missense NM_001406570.1:c.587A>T NP_001393499.1:p.Asp196Val missense NM_001406571.1:c.587A>T NP_001393500.1:p.Asp196Val missense NM_001406572.1:c.587A>T NP_001393501.1:p.Asp196Val missense NM_001406573.1:c.587A>T NP_001393502.1:p.Asp196Val missense NM_001406574.1:c.587A>T NP_001393503.1:p.Asp196Val missense NM_001406575.1:c.587A>T NP_001393504.1:p.Asp196Val missense NM_001406576.1:c.587A>T NP_001393505.1:p.Asp196Val missense NM_001406577.1:c.587A>T NP_001393506.1:p.Asp196Val missense NM_001406578.1:c.587A>T NP_001393507.1:p.Asp196Val missense NM_001406579.1:c.587A>T NP_001393508.1:p.Asp196Val missense NM_001406580.1:c.587A>T NP_001393509.1:p.Asp196Val missense NM_001406581.1:c.587A>T NP_001393510.1:p.Asp196Val missense NM_001406582.1:c.587A>T NP_001393511.1:p.Asp196Val missense NM_001406583.1:c.587A>T NP_001393512.1:p.Asp196Val missense NM_001406584.1:c.503A>T NP_001393513.1:p.Asp168Val missense NM_001406585.1:c.503A>T NP_001393514.1:p.Asp168Val missense NM_001406586.1:c.503A>T NP_001393515.1:p.Asp168Val missense NM_001406587.1:c.503A>T NP_001393516.1:p.Asp168Val missense NM_001406588.1:c.503A>T NP_001393517.1:p.Asp168Val missense NR_176211.1:n.1155A>T NR_176212.1:n.1155A>T NR_176213.1:n.1155A>T NC_000010.11:g.86912296A>T NC_000010.10:g.88672053A>T NG_009362.1:g.160658A>T LRG_298:g.160658A>T LRG_298t1:c.587A>T LRG_298p1:p.Asp196Val - Protein change
- D212V, D168V, D221V, D196V
- Other names
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- Canonical SPDI
- NC_000010.11:86912295:A: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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Jul 11, 2022 | RCV002353509.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Sep 19, 2023 | RCV003597431.2 |
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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Uncertain significance
(Sep 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004324441.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this … (more)
This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 1750242). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 196 of the BMPR1A protein (p.Asp196Val). (less)
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Uncertain significance
(Jul 11, 2022)
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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: SCV002652807.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.D196V variant (also known as c.587A>T), located in coding exon 6 of the BMPR1A gene, results from an A to T substitution at nucleotide … (more)
The p.D196V variant (also known as c.587A>T), located in coding exon 6 of the BMPR1A gene, results from an A to T substitution at nucleotide position 587. The aspartic acid at codon 196 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The p.D196V variant (also known as c.587A>T), located in coding exon 6 of the BMPR1A gene, results from an A to T substitution at nucleotide position 587. The aspartic acid at codon 196 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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 not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 1750242). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 196 of the BMPR1A protein (p.Asp196Val).
Comment:
The p.D196V variant (also known as c.587A>T), located in coding exon 6 of the BMPR1A gene, results from an A to T substitution at nucleotide position 587. The aspartic acid at codon 196 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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 Sep 29, 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.