VCV002851621.2 - ClinVar

NM_004329.3(BMPR1A):c.67+1G>A

Germline

Classification

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)

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.

Pathogenic/Likely pathogenic

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.67+1G>A

Variation ID: 2851621 Accession: VCV002851621.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q23.2 10: 86876086 (GRCh38) [ NCBI UCSC ] 10: 88635843 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Feb 20, 2024	Jun 17, 2024	Jan 3, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004329.3:c.67+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001406559.1:c.67+1G>A		splice donor
NM_001406560.1:c.67+1G>A		splice donor
NM_001406561.1:c.67+1G>A		splice donor
NM_001406562.1:c.67+1G>A		splice donor
NM_001406563.1:c.67+1G>A		splice donor
NM_001406564.1:c.67+1G>A		splice donor
NM_001406565.1:c.67+1G>A		splice donor
NM_001406566.1:c.67+1G>A		splice donor
NM_001406567.1:c.67+1G>A		splice donor
NM_001406568.1:c.67+1G>A		splice donor
NM_001406569.1:c.67+1G>A		splice donor
NM_001406570.1:c.67+1G>A		splice donor
NM_001406571.1:c.67+1G>A		splice donor
NM_001406572.1:c.67+1G>A		splice donor
NM_001406573.1:c.67+1G>A		splice donor
NM_001406574.1:c.67+1G>A		splice donor
NM_001406575.1:c.67+1G>A		splice donor
NM_001406576.1:c.67+1G>A		splice donor
NM_001406577.1:c.67+1G>A		splice donor
NM_001406578.1:c.67+1G>A		splice donor
NM_001406579.1:c.67+1G>A		splice donor
NM_001406580.1:c.67+1G>A		splice donor
NM_001406581.1:c.67+1G>A		splice donor
NM_001406582.1:c.67+1G>A		splice donor
NM_001406583.1:c.67+1G>A		splice donor
NM_001406584.1:c.-17-13976G>A		intron variant
NM_001406585.1:c.-17-13976G>A		intron variant
NM_001406586.1:c.-12-13981G>A		intron variant
NM_001406587.1:c.-17-13976G>A		intron variant
NM_001406588.1:c.-13+1G>A		splice donor
NM_001406589.1:c.67+1G>A		splice donor
NC_000010.11:g.86876086G>A
NC_000010.10:g.88635843G>A
NG_009362.1:g.124448G>A
LRG_298:g.124448G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000010.11:86876085:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

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
Gene	OMIM	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	2328	2424

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.
Juvenile polyposis syndrome	Pathogenic (1)	criteria provided, single submitter	Aug 16, 2023	RCV003763295.2
Polyposis syndrome, hereditary mixed, 2	Likely pathogenic (1)	criteria provided, single submitter	Jan 3, 2024	RCV004573171.1

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.
Pathogenic (Aug 16, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Juvenile polyposis syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004451547.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Comment: For these reasons, this variant has been classified as Pathogenic. Other variant(s) that result in initiator codon loss have been determined to be pathogenic (Invitae). … (more) For these reasons, this variant has been classified as Pathogenic. Other variant(s) that result in initiator codon loss have been determined to be pathogenic (Invitae). This suggests that this variant may also be clinically significant and likely to be disease-causing. Studies have shown that disruption of this splice site results in skipping of part of exon 3, and is expected to result in the loss of the initiator methionine (Invitae). 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 affects a donor splice site in intron 3 of the BMPR1A gene. RNA analysis indicates that disruption of this splice site induces altered splicing and is likely to result in the loss of the initiator methionine. (less)
Likely pathogenic (Jan 03, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Polyposis syndrome, hereditary mixed, 2 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV005058181.1 First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024

Comment:

For these reasons, this variant has been classified as Pathogenic. Other variant(s) that result in initiator codon loss have been determined to be pathogenic (Invitae). This suggests that this variant may also be clinically significant and likely to be disease-causing. Studies have shown that disruption of this splice site results in skipping of part of exon 3, and is expected to result in the loss of the initiator methionine (Invitae). 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 affects a donor splice site in intron 3 of the BMPR1A gene. RNA analysis indicates that disruption of this splice site induces altered splicing and is likely to result in the loss of the initiator methionine.

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:

Citations for germline classification of this variant

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 ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_004329.3(BMPR1A):c.67+1G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...