This missense variant replaces glutamic acid with aspartic acid at codon 88 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.264A>T (p.Glu88Asp)
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.264A>T (p.Glu88Asp)
Variation ID: 1794294 Accession: VCV001794294.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86892160 (GRCh38) [ NCBI UCSC ] 10: 88651917 (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 Aug 11, 2024 Jun 13, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004329.3:c.264A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Glu88Asp missense NM_001406559.1:c.264A>T NP_001393488.1:p.Glu88Asp missense NM_001406560.1:c.264A>T NP_001393489.1:p.Glu88Asp missense NM_001406561.1:c.264A>T NP_001393490.1:p.Glu88Asp missense NM_001406562.1:c.264A>T NP_001393491.1:p.Glu88Asp missense NM_001406563.1:c.264A>T NP_001393492.1:p.Glu88Asp missense NM_001406564.1:c.264A>T NP_001393493.1:p.Glu88Asp missense NM_001406565.1:c.264A>T NP_001393494.1:p.Glu88Asp missense NM_001406566.1:c.264A>T NP_001393495.1:p.Glu88Asp missense NM_001406567.1:c.264A>T NP_001393496.1:p.Glu88Asp missense NM_001406568.1:c.264A>T NP_001393497.1:p.Glu88Asp missense NM_001406569.1:c.264A>T NP_001393498.1:p.Glu88Asp missense NM_001406570.1:c.264A>T NP_001393499.1:p.Glu88Asp missense NM_001406571.1:c.264A>T NP_001393500.1:p.Glu88Asp missense NM_001406572.1:c.264A>T NP_001393501.1:p.Glu88Asp missense NM_001406573.1:c.264A>T NP_001393502.1:p.Glu88Asp missense NM_001406574.1:c.264A>T NP_001393503.1:p.Glu88Asp missense NM_001406575.1:c.264A>T NP_001393504.1:p.Glu88Asp missense NM_001406576.1:c.264A>T NP_001393505.1:p.Glu88Asp missense NM_001406577.1:c.264A>T NP_001393506.1:p.Glu88Asp missense NM_001406578.1:c.264A>T NP_001393507.1:p.Glu88Asp missense NM_001406579.1:c.264A>T NP_001393508.1:p.Glu88Asp missense NM_001406580.1:c.264A>T NP_001393509.1:p.Glu88Asp missense NM_001406581.1:c.264A>T NP_001393510.1:p.Glu88Asp missense NM_001406582.1:c.264A>T NP_001393511.1:p.Glu88Asp missense NM_001406583.1:c.264A>T NP_001393512.1:p.Glu88Asp missense NM_001406584.1:c.180A>T NP_001393513.1:p.Glu60Asp missense NM_001406585.1:c.180A>T NP_001393514.1:p.Glu60Asp missense NM_001406586.1:c.180A>T NP_001393515.1:p.Glu60Asp missense NM_001406587.1:c.180A>T NP_001393516.1:p.Glu60Asp missense NM_001406588.1:c.180A>T NP_001393517.1:p.Glu60Asp missense NM_001406589.1:c.264A>T NP_001393518.1:p.Glu88Asp missense NR_176211.1:n.832A>T NR_176212.1:n.832A>T NR_176213.1:n.832A>T NC_000010.11:g.86892160A>T NC_000010.10:g.88651917A>T NG_009362.1:g.140522A>T LRG_298:g.140522A>T LRG_298t1:c.264A>T LRG_298p1:p.Glu88Asp - Protein change
- E88D, E60D
- Other names
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- Canonical SPDI
- NC_000010.11:86892159: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 (2) |
criteria provided, multiple submitters, no conflicts
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Jun 13, 2024 | RCV002428680.4 |
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
(Nov 07, 2023)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV004360046.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces glutamic acid with aspartic acid at codon 88 of the BMPR1A protein. Computational prediction suggests that this variant may not impact … (more)
This missense variant replaces glutamic acid with aspartic acid at codon 88 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jun 13, 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: SCV002743424.3
First in ClinVar: Nov 29, 2022 Last updated: Aug 11, 2024 |
Comment:
The p.E88D variant (also known as c.264A>T), located in coding exon 3 of the BMPR1A gene, results from an A to T substitution at nucleotide … (more)
The p.E88D variant (also known as c.264A>T), located in coding exon 3 of the BMPR1A gene, results from an A to T substitution at nucleotide position 264. The glutamic acid at codon 88 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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)
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Comment:
Comment:
The p.E88D variant (also known as c.264A>T), located in coding exon 3 of the BMPR1A gene, results from an A to T substitution at nucleotide position 264. The glutamic acid at codon 88 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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 missense variant replaces glutamic acid with aspartic acid at codon 88 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
The p.E88D variant (also known as c.264A>T), located in coding exon 3 of the BMPR1A gene, results from an A to T substitution at nucleotide position 264. The glutamic acid at codon 88 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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 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.