BMPR1A: BP4, BP7
ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.618A>G (p.Leu206=)
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.
(15)
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.
Benign/Likely benign
15
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004329.3(BMPR1A):c.618A>G (p.Leu206=)
Variation ID: 132739 Accession: VCV000132739.41
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86912327 (GRCh38) [ NCBI UCSC ] 10: 88672084 (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 1, 2016 Oct 20, 2024 Jan 31, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004329.3:c.618A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Leu206= synonymous NC_000010.11:g.86912327A>G NC_000010.10:g.88672084A>G NG_009362.1:g.160689A>G LRG_298:g.160689A>G LRG_298t1:c.618A>G LRG_298p1:p.Leu206= - Protein change
- -
- Other names
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p.L206L:CTA>CTG
- Canonical SPDI
- NC_000010.11:86912326:A:G
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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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0.00160 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00257
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00300
The Genome Aggregation Database (gnomAD), exomes 0.00064
Exome Aggregation Consortium (ExAC) 0.00073
1000 Genomes Project 30x 0.00156
1000 Genomes Project 0.00160
Trans-Omics for Precision Medicine (TOPMed) 0.00252
- 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. |
|||
| 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. |
|---|---|---|---|---|
| Likely benign (1) |
criteria provided, single submitter
|
Nov 17, 2015 | RCV000119191.14 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 6, 2020 | RCV000123857.14 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000212146.15 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jun 1, 2023 | RCV000758775.20 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV001507159.11 |
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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|---|---|---|---|---|---|
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Benign
(Mar 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806606.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
|
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Benign
(May 25, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000887606.2
First in ClinVar: Mar 14, 2019 Last updated: Jan 03, 2022 |
|
|
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Likely benign
(Nov 17, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000487813.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
|
|
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Likely benign
(Jun 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004127020.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
BMPR1A: BP4, BP7
Number of individuals with the variant: 1
|
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Benign
(Feb 17, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167200.11
First in ClinVar: Jun 23, 2014 Last updated: Jun 01, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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Benign
(May 29, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000861274.1
First in ClinVar: Sep 13, 2018 Last updated: Sep 13, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
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Benign
(Mar 22, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002065572.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
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Benign
(Nov 06, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002531107.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
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Benign
(Mar 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000682904.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
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Benign
(Mar 02, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004019454.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
|
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Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004027586.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
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Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000153928.13
First in ClinVar: Jun 03, 2014 Last updated: Feb 28, 2024 |
|
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Likely benign
(Dec 21, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213123.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
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Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005221840.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001551252.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The BMPR1A p.Leu206= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP … (more)
The BMPR1A p.Leu206= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs55992440) as "With other allele", and ClinVar (classified as benign by Invitae, GeneDx and five other submitters; as likely benign by two submitters). The variant was identified in control databases in 226 of 277110 chromosomes (1 homozygous) at a frequency of 0.0008 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 199 of 24032 chromosomes (freq: 0.008), Other in 1 of 6458 chromosomes (freq: 0.0002), Latino in 25 of 34400 chromosomes (freq: 0.0008), European in 1 of 126628 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Leu206= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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Comment:
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
The BMPR1A p.Leu206= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs55992440) as "With other allele", and ClinVar (classified as benign by Invitae, GeneDx and five other submitters; as likely benign by two submitters). The variant was identified in control databases in 226 of 277110 chromosomes (1 homozygous) at a frequency of 0.0008 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 199 of 24032 chromosomes (freq: 0.008), Other in 1 of 6458 chromosomes (freq: 0.0002), Latino in 25 of 34400 chromosomes (freq: 0.0008), European in 1 of 126628 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Leu206= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
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:
BMPR1A: BP4, BP7
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
The BMPR1A p.Leu206= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs55992440) as "With other allele", and ClinVar (classified as benign by Invitae, GeneDx and five other submitters; as likely benign by two submitters). The variant was identified in control databases in 226 of 277110 chromosomes (1 homozygous) at a frequency of 0.0008 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 199 of 24032 chromosomes (freq: 0.008), Other in 1 of 6458 chromosomes (freq: 0.0002), Latino in 25 of 34400 chromosomes (freq: 0.0008), European in 1 of 126628 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Leu206= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Patterns of somatic mutation in human cancer genomes. | Greenman C | Nature | 2007 | PMID: 17344846 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BMPR1A | - | - | - | - |
| http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/?chr=10&from=88672084&to=88672084 | - | - | - | - |
Text-mined citations for rs55992440 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 20, 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.