Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 245 of the BMPR1A protein (p.Tyr245Cys).
ClinVar Genomic variation as it relates to human health
NM_004329.3(BMPR1A):c.734A>G (p.Tyr245Cys)
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.
(3)
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
3
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.734A>G (p.Tyr245Cys)
Variation ID: 1758439 Accession: VCV001758439.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86917192 (GRCh38) [ NCBI UCSC ] 10: 88676949 (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 Nov 3, 2024 Feb 2, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004329.3:c.734A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004320.2:p.Tyr245Cys missense NM_001406559.1:c.809A>G NP_001393488.1:p.Tyr270Cys missense NM_001406560.1:c.782A>G NP_001393489.1:p.Tyr261Cys missense NM_001406561.1:c.734A>G NP_001393490.1:p.Tyr245Cys missense NM_001406562.1:c.734A>G NP_001393491.1:p.Tyr245Cys missense NM_001406563.1:c.734A>G NP_001393492.1:p.Tyr245Cys missense NM_001406564.1:c.734A>G NP_001393493.1:p.Tyr245Cys missense NM_001406565.1:c.734A>G NP_001393494.1:p.Tyr245Cys missense NM_001406566.1:c.734A>G NP_001393495.1:p.Tyr245Cys missense NM_001406567.1:c.734A>G NP_001393496.1:p.Tyr245Cys missense NM_001406568.1:c.734A>G NP_001393497.1:p.Tyr245Cys missense NM_001406569.1:c.734A>G NP_001393498.1:p.Tyr245Cys missense NM_001406570.1:c.734A>G NP_001393499.1:p.Tyr245Cys missense NM_001406571.1:c.734A>G NP_001393500.1:p.Tyr245Cys missense NM_001406572.1:c.734A>G NP_001393501.1:p.Tyr245Cys missense NM_001406573.1:c.734A>G NP_001393502.1:p.Tyr245Cys missense NM_001406574.1:c.734A>G NP_001393503.1:p.Tyr245Cys missense NM_001406575.1:c.734A>G NP_001393504.1:p.Tyr245Cys missense NM_001406576.1:c.734A>G NP_001393505.1:p.Tyr245Cys missense NM_001406577.1:c.734A>G NP_001393506.1:p.Tyr245Cys missense NM_001406578.1:c.734A>G NP_001393507.1:p.Tyr245Cys missense NM_001406579.1:c.734A>G NP_001393508.1:p.Tyr245Cys missense NM_001406580.1:c.734A>G NP_001393509.1:p.Tyr245Cys missense NM_001406581.1:c.734A>G NP_001393510.1:p.Tyr245Cys missense NM_001406582.1:c.734A>G NP_001393511.1:p.Tyr245Cys missense NM_001406583.1:c.728A>G NP_001393512.1:p.Tyr243Cys missense NM_001406584.1:c.650A>G NP_001393513.1:p.Tyr217Cys missense NM_001406585.1:c.650A>G NP_001393514.1:p.Tyr217Cys missense NM_001406586.1:c.650A>G NP_001393515.1:p.Tyr217Cys missense NM_001406587.1:c.650A>G NP_001393516.1:p.Tyr217Cys missense NM_001406588.1:c.650A>G NP_001393517.1:p.Tyr217Cys missense NM_001406589.1:c.392A>G NP_001393518.1:p.Tyr131Cys missense NR_176211.1:n.1302A>G NR_176212.1:n.1302A>G NR_176213.1:n.1302A>G NC_000010.11:g.86917192A>G NC_000010.10:g.88676949A>G NG_009362.1:g.165554A>G LRG_298:g.165554A>G LRG_298t1:c.734A>G LRG_298p1:p.Tyr245Cys - Protein change
- Y243C, Y270C, Y217C, Y245C, Y131C, Y261C
- Other names
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- Canonical SPDI
- NC_000010.11:86917191: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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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. |
|||
| 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
|
Mar 3, 2022 | RCV002380235.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 19, 2022 | RCV003763141.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 2, 2024 | RCV004774675.1 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Nov 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Juvenile polyposis syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004413856.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to … (more)
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 245 of the BMPR1A protein (p.Tyr245Cys). (less)
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Uncertain significance
(Mar 03, 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
|
Ambry Genetics
Accession: SCV002671102.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.Y245C variant (also known as c.734A>G), located in coding exon 7 of the BMPR1A gene, results from an A to G substitution at nucleotide … (more)
The p.Y245C variant (also known as c.734A>G), located in coding exon 7 of the BMPR1A gene, results from an A to G substitution at nucleotide position 734. The tyrosine at codon 245 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Feb 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV005386819.1
First in ClinVar: Nov 03, 2024 Last updated: Nov 03, 2024 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235019) (less)
|
Comment:
Comment:
The p.Y245C variant (also known as c.734A>G), located in coding exon 7 of the BMPR1A gene, results from an A to G substitution at nucleotide position 734. The tyrosine at codon 245 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235019)
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:
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 245 of the BMPR1A protein (p.Tyr245Cys).
Comment:
The p.Y245C variant (also known as c.734A>G), located in coding exon 7 of the BMPR1A gene, results from an A to G substitution at nucleotide position 734. The tyrosine at codon 245 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235019)
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 Nov 03, 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.