NM_003995.4(NPR2):c.2738dup (p.Met913fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 2023
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:: RCV003806068.2

Allele description [Variation Report for NM_003995.4(NPR2):c.2738dup (p.Met913fs)]

NM_003995.4(NPR2):c.2738dup (p.Met913fs)

Genes:

NPR2:natriuretic peptide receptor 2 [Gene - OMIM - HGNC]
SPAG8:sperm associated antigen 8 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_003995.4(NPR2):c.2738dup (p.Met913fs)

HGVS:

NC_000009.12:g.35808534dup
NG_009249.1:g.21126dup
NG_047141.1:g.8739dup
NM_001366760.2:c.1201-228dup
NM_001378923.1:c.2747dup
NM_003995.4:c.2738dupMANE SELECT
NM_172312.2:c.1373-228dup
NP_001365852.1:p.Met916fs
NP_003986.2:p.Met913fs
NC_000009.11:g.35808530_35808531insT
NC_000009.11:g.35808531dup

Protein change:

M913fs

Molecular consequence:

NM_001378923.1:c.2747dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003995.4:c.2738dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366760.2:c.1201-228dup - intron variant - [Sequence Ontology: SO:0001627]
NM_172312.2:c.1373-228dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Acromesomelic dysplasia 1, Maroteaux type (AMD1)
Synonyms:: Acromesomelic dwarfism Maroteux type; ST. HELENA DYSPLASIA; Acromesomelic dysplasia, Maroteaux type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011275; MedGen: C1864356; Orphanet: 40; OMIM: 602875

Name:: Tall stature-scoliosis-macrodactyly of the great toes syndrome
Synonyms:: Epiphyseal chondrodysplasia, miura type
Identifiers:: MONDO: MONDO:0014401; MedGen: C4014690; Orphanet: 329191; OMIM: 615923

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004589430	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15146390, 15572448, 16384845, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004589430

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux.

Bartels CF, Bükülmez H, Padayatti P, Rhee DK, van Ravenswaaij-Arts C, Pauli RM, Mundlos S, Chitayat D, Shih LY, Al-Gazali LI, Kant S, Cole T, Morton J, Cormier-Daire V, Faivre L, Lees M, Kirk J, Mortier GR, Leroy J, Zabel B, Kim CA, Crow Y, et al.

Am J Hum Genet. 2004 Jul;75(1):27-34. Epub 2004 May 14.

PubMed [citation]

PMID:: 15146390
PMCID:: PMC1182004

Critical roles of the guanylyl cyclase B receptor in endochondral ossification and development of female reproductive organs.

Tamura N, Doolittle LK, Hammer RE, Shelton JM, Richardson JA, Garbers DL.

Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17300-5. Epub 2004 Nov 30.

PubMed [citation]

PMID:: 15572448
PMCID:: PMC534612

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004589430.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Met913Ilefs*40) in the NPR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPR2 are known to be pathogenic (PMID: 15146390, 15572448, 16384845). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NPR2-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 30, 2024

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