NM_003995.4(NPR2):c.2762G>A (p.Arg921Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 29, 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:: RCV001992975.13

Allele description [Variation Report for NM_003995.4(NPR2):c.2762G>A (p.Arg921Gln)]

NM_003995.4(NPR2):c.2762G>A (p.Arg921Gln)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_003995.4(NPR2):c.2762G>A (p.Arg921Gln)

HGVS:

NC_000009.12:g.35808558G>A
NG_009249.1:g.21150G>A
NG_047141.1:g.8715C>T
NM_001366760.2:c.1201-252C>T
NM_001378923.1:c.2771G>A
NM_003995.4:c.2762G>AMANE SELECT
NM_172312.2:c.1373-252C>T
NP_001365852.1:p.Arg924Gln
NP_003986.2:p.Arg921Gln
NC_000009.11:g.35808555G>A

Protein change:

R921Q

Links:

dbSNP: rs770276670

NCBI 1000 Genomes Browser:

rs770276670

Molecular consequence:

NM_001366760.2:c.1201-252C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_172312.2:c.1373-252C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001378923.1:c.2771G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003995.4:c.2762G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002235880	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31960617, 26567084, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235880

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2023)

germline

clinical testing

PubMed (3)
[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

Role of NPR2 mutation in idiopathic short stature: Identification of two novel mutations.

Hwang IT, Mizuno Y, Amano N, Lee HJ, Shim YS, Nam HK, Rhie YJ, Yang S, Lee KH, Hasegawa T, Kang MJ.

Mol Genet Genomic Med. 2020 Mar;8(3):e1146. doi: 10.1002/mgg3.1146. Epub 2020 Jan 20.

PubMed [citation]

PMID:: 31960617
PMCID:: PMC7057090

Acromesomelic dysplasia, type maroteaux caused by novel loss-of-function mutations of the NPR2 gene: Three case reports.

Wang W, Song MH, Miura K, Fujiwara M, Nawa N, Ohata Y, Kitaoka T, Kubota T, Namba N, Jin DK, Kim OH, Ozono K, Cho TJ.

Am J Med Genet A. 2016 Feb;170A(2):426-434. doi: 10.1002/ajmg.a.37463. Epub 2015 Nov 14.

PubMed [citation]

PMID:: 26567084

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002235880.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 921 of the NPR2 protein (p.Arg921Gln). This variant is present in population databases (rs770276670, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive acromesomelic dysplasia, type Maroteaux and/or clinical features of autosomal dominant short stature (PMID: 26567084, 31960617). ClinVar contains an entry for this variant (Variation ID: 1450866). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NPR2 protein function. Experimental studies have shown that this missense change affects NPR2 function (PMID: 26567084). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 26, 2024

ClinVar

Relating variation to medicine