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

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:
RCV000190431.4

Allele description [Variation Report for NM_003995.4(NPR2):c.328C>T (p.Arg110Cys)]

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 (SNSK1)
Synonyms:
SHORT STATURE WITH NONSPECIFIC SKELETAL ABNORMALITIES 1
Identifiers:
MONDO: MONDO:0014551; MedGen: C4225399; OMIM: 616255

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000244271OMIM
no assertion criteria provided
Pathogenic
(Apr 1, 2014) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature 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, SCV000244271.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

By direct sequencing of the NPR2 gene in 101 unrelated Japanese patients with short stature (SNSK1; 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.

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

Last Updated: Oct 8, 2024