NM_003995.4(NPR2):c.664C>T (p.Arg222Cys) AND multiple conditions

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

Germline classification:: Uncertain significance (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:: RCV003059297.2

Allele description

NM_003995.4(NPR2):c.664C>T (p.Arg222Cys)

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.664C>T (p.Arg222Cys)

HGVS:

NC_000009.12:g.35793072C>T
NG_009249.1:g.5664C>T
NM_001378923.1:c.664C>T
NM_003995.4:c.664C>TMANE SELECT
NP_001365852.1:p.Arg222Cys
NP_003986.2:p.Arg222Cys
NC_000009.11:g.35793069C>T

Protein change:

R222C

Molecular consequence:

NM_001378923.1:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003995.4:c.664C>T - 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
SCV003331838	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 14, 2023)	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

SCV003331838

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 14, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003331838.2

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with NPR2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 222 of the NPR2 protein (p.Arg222Cys).

#	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: Mar 5, 2024

ClinVar

Relating variation to medicine