NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 16, 2017
Review status:: criteria provided, conflicting classifications

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:: RCV000196055.4

Allele description [Variation Report for NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr)]

NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr)

Gene:

BMPR2:bone morphogenetic protein receptor type 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.2

Genomic location:

Preferred name:

NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr)

Other names:

p.R266T:AGA>ACA; NM_001204.7(BMPR2):c.797G>C; p.Arg266Thr

HGVS:

NC_000002.12:g.202518997G>C
NG_009363.1:g.147671G>C
NM_001204.7:c.797G>CMANE SELECT
NP_001195.2:p.Arg266Thr
LRG_712t1:c.797G>C
LRG_712:g.147671G>C
LRG_712p1:p.R266T
NC_000002.11:g.203383720G>C
NM_001204.6:c.797G>C
NP_001195.2:p.R266T

Protein change:

R266T

Links:

dbSNP: rs374694591

NCBI 1000 Genomes Browser:

rs374694591

Molecular consequence:

NM_001204.7:c.797G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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txid3073639[Organism:noexp] (1147)
Protein
AKR1B1P5 aldo-keto reductase family 1 member B1 pseudogene 5 [Homo sapiens]
AKR1B1P5 aldo-keto reductase family 1 member B1 pseudogene 5 [Homo sapiens]
Gene ID:390482

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000249642	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 2, 2014)	germline	clinical testing	Citation Link,
SCV000610429	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 16, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000249642

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 2, 2014)

germline

clinical testing

Citation Link,

SCV000610429

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 16, 2017)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	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 GeneDx, SCV000249642.11

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

Description

p.Arg266Thr (AGA>ACA): c.797 G>C in exon 6 of the BMPR2 gene (NM_001204.6). The R266T mutation in the BMPR2 gene has been reported in one individual diagnosed with PAH and was absent from 300 control chromosomes; however, no additional clinical information or segregation studies were provided (Machado et al., 2006). R266T results in a semi-conservative amino acid substitution as these residues share similar properties, but differs in size, charge, or other properties which may impact secondary structure. This substitution occurs at a position that is conserved across species. Mutations in nearby residues (D264N, M273R) have been reported in association with PAH, further supporting the functional importance of this region of the protein. Furthermore, the R266T variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. In summary, R266T in the BMPR2 gene is interpreted as a disease-causing mutation. This variant was found in PAH-ARRHYTHMIA

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

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000610429.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.000185	not provided	not provided

Last Updated: Oct 13, 2024

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