NM_004329.3(BMPR1A):c.730C>T (p.Arg244Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 5, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000850053.5

Allele description [Variation Report for NM_004329.3(BMPR1A):c.730C>T (p.Arg244Ter)]

NM_004329.3(BMPR1A):c.730C>T (p.Arg244Ter)

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.730C>T (p.Arg244Ter)

HGVS:

NC_000010.11:g.86917188C>T
NG_009362.1:g.165550C>T
NM_004329.3:c.730C>TMANE SELECT
NP_004320.2:p.Arg244Ter
NP_004320.2:p.Arg244Ter
LRG_298t1:c.730C>T
LRG_298:g.165550C>T
LRG_298p1:p.Arg244Ter
NC_000010.10:g.88676945C>T
NM_004329.2:c.730C>T

Protein change:

R244*

Links:

dbSNP: rs759363072

NCBI 1000 Genomes Browser:

rs759363072

Molecular consequence:

NM_004329.3:c.730C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000992195	Academic Department of Medical Genetics, University of Cambridge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 26, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV001188599	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 5, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000992195

Academic Department of Medical Genetics, University of Cambridge

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 26, 2018)

germline

research

PubMed (1)
[See all records that cite this PMID]

SCV001188599

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 5, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Academic Department of Medical Genetics, University of Cambridge, SCV000992195.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

Description

Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	See 1

Co-occurrences

#	Zygosity	Alleles	Number of Observations
1		NM_000535:c.741_742insTGAAG; NP_000526:p.Ser248Ter

From Ambry Genetics, SCV001188599.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.R244* pathogenic mutation (also known as c.730C>T), located in coding exon 7 of the BMPR1A gene, results from a C to T substitution at nucleotide position 730. This changes the amino acid from an arginine to a stop codon within coding exon 7. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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