NM_003995.4(NPR2):c.328C>T (p.Arg110Cys) AND Short stature with nonspecific skeletal abnormalities

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 1, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000190431.3

Allele description

NM_003995.4(NPR2):c.328C>T (p.Arg110Cys)

Gene:

NPR2:natriuretic peptide receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_003995.4(NPR2):c.328C>T (p.Arg110Cys)

HGVS:

NC_000009.12:g.35792736C>T
NG_009249.1:g.5328C>T
NM_001378923.1:c.328C>T
NM_003995.4:c.328C>TMANE SELECT
NP_001365852.1:p.Arg110Cys
NP_003986.2:p.Arg110Cys
NP_003986.2:p.Arg110Cys
NC_000009.11:g.35792733C>T
NM_003995.3:c.328C>T
NM_003995.3:c.328C>T
P20594:p.Arg110Cys

Protein change:

R110C; ARG110CYS

Links:

UniProtKB: P20594#VAR_074679; OMIM: 108961.0012; dbSNP: rs758478717

NCBI 1000 Genomes Browser:

rs758478717

Molecular consequence:

NM_001378923.1:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003995.4:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Short stature with nonspecific skeletal abnormalities (SNSK)
Identifiers:: MONDO: MONDO:0014551; MedGen: C4225399; OMIM: 616255

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000244271	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000244271

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2014)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Identification and functional characterization of two novel NPR2 mutations in Japanese patients with short stature.

Amano N, Mukai T, Ito Y, Narumi S, Tanaka T, Yokoya S, Ogata T, Hasegawa T.

J Clin Endocrinol Metab. 2014 Apr;99(4):E713-8. doi: 10.1210/jc.2013-3525. Epub 2014 Jan 28.

PubMed [citation]

PMID:: 24471569

Details of each submission

From OMIM, SCV000244271.2

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

Description

By direct sequencing of the NPR2 gene in 101 unrelated Japanese patients with short stature (SNSK; 616255), Amano et al. (2014) identified a heterozygous c.328C-T transition, resulting in an arg110-to-cys (R110C) mutation in 1 proband (adult height -2.8 SD) and his mother (adult height -1.3 SD). The father and 1 sib did not carry the mutation; another sib was not tested. The mutation was not present in the dbSNP or 1000 Genomes Project databases or in 100 Japanese control individuals. Coexpression of the mutant and wildtype led to a significant loss in the CNP-dependent cGMP response compared with that of the empty vector and wildtype, indicating a dominant-negative effect. Western blot analysis showed that the R110C mutant did not exist in the O-glycosylated form and did not show cell surface expression when compared to the Q417E (108961.0013) mutant. The R110C variant colocalized with an endoplasmic reticulum (ER) marker, suggesting that this variant causes defective trafficking from the ER to the Golgi apparatus.

#	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	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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