NM_003995.4(NPR2):c.1249C>G (p.Gln417Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 7, 2022
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:: RCV002514081.3

Allele description [Variation Report for NM_003995.4(NPR2):c.1249C>G (p.Gln417Glu)]

NM_003995.4(NPR2):c.1249C>G (p.Gln417Glu)

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.1249C>G (p.Gln417Glu)

HGVS:

NC_000009.12:g.35800739C>G
NG_009249.1:g.13331C>G
NM_001378923.1:c.1249C>G
NM_003995.4:c.1249C>GMANE SELECT
NP_001365852.1:p.Gln417Glu
NP_003986.2:p.Gln417Glu
NC_000009.11:g.35800736C>G
P20594:p.Gln417Glu

Protein change:

Q417E; GLN417GLU

Links:

UniProtKB: P20594#VAR_074682; OMIM: 108961.0013; dbSNP: rs796065356

NCBI 1000 Genomes Browser:

rs796065356

Molecular consequence:

NM_001378923.1:c.1249C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003995.4:c.1249C>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003297399	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 7, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30602027, 24471569, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003297399

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 7, 2022)

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

Multigene Sequencing Analysis of Children Born Small for Gestational Age With Isolated Short Stature.

Freire BL, Homma TK, Funari MFA, Lerario AM, Vasques GA, Malaquias AC, Arnhold IJP, Jorge AAL.

J Clin Endocrinol Metab. 2019 Jun 1;104(6):2023-2030. doi: 10.1210/jc.2018-01971.

PubMed [citation]

PMID:: 30602027

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003297399.2

#	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 glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 417 of the NPR2 protein (p.Gln417Glu). This variant is present in population databases (rs796065356, gnomAD no frequency). This missense change has been observed in individual(s) with short stature (PMID: 24471569, 30602027). ClinVar contains an entry for this variant (Variation ID: 208360). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). Experimental studies have shown that this missense change affects NPR2 function (PMID: 24471569). 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: Oct 8, 2024

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