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NM_004329.3(BMPR1A):c.3G>A (p.Met1Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 5, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001021627.3

Allele description [Variation Report for NM_004329.3(BMPR1A):c.3G>A (p.Met1Ile)]

NM_004329.3(BMPR1A):c.3G>A (p.Met1Ile)

Gene:
BMPR1A:bone morphogenetic protein receptor type 1A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.2
Genomic location:
Preferred name:
NM_004329.3(BMPR1A):c.3G>A (p.Met1Ile)
HGVS:
  • NC_000010.11:g.86876021G>A
  • NG_009362.1:g.124383G>A
  • NM_004329.3:c.3G>AMANE SELECT
  • NP_004320.2:p.Met1Ile
  • LRG_298t1:c.3G>A
  • LRG_298:g.124383G>A
  • NC_000010.10:g.88635778G>A
  • NM_004329.2:c.3G>A
Protein change:
M1I
Links:
dbSNP: rs869312758
NCBI 1000 Genomes Browser:
rs869312758
Molecular consequence:
  • NM_004329.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_004329.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001183267Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 5, 2019) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis.

Calva-Cerqueira D, Chinnathambi S, Pechman B, Bair J, Larsen-Haidle J, Howe JR.

Clin Genet. 2009 Jan;75(1):79-85. doi: 10.1111/j.1399-0004.2008.01091.x. Epub 2008 Sep 24.

PubMed [citation]
PMID:
18823382

BMPR1A mutations in juvenile polyposis affect cellular localization.

Howe JR, Dahdaleh FS, Carr JC, Wang D, Sherman SK, Howe JR.

J Surg Res. 2013 Oct;184(2):739-45. doi: 10.1016/j.jss.2013.01.015. Epub 2013 Feb 1.

PubMed [citation]
PMID:
23433720
PMCID:
PMC3683109

Details of each submission

From Ambry Genetics, SCV001183267.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.M1? variant (also known as c.3G>A) is located in coding exon 1 of the BMPR1A gene and results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. There is an in-frame methionine 29 amino acids downstream from this initiation site which may result in an N-terminal truncation; however, direct evidence is unavailable. Based on an internal structural analysis, this N-terminal truncation is anticipated to result in disruption of the BMPR1A signaling motif. This variant was identified in a proband meeting clinical diagnostic criteria for juvenile polyposis syndrome (Ambry internal data). Other variants that affect the initiation codon of BMPR1A, c.1A>C and c.1A>G, have been identified in individuals with juvenile polyposis (Calva-Cerqueira D. et al. Clin. Genet. 2009 Jan;75:79-85; Howe JR et al. J. Surg. Res. 2013 Oct;184:739-45; Ambry internal data). In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024