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NM_005529.7(HSPG2):c.13033G>A (p.Gly4345Arg) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:
Dec 31, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV000518544.16

Allele description

NM_005529.7(HSPG2):c.13033G>A (p.Gly4345Arg)

Genes:
HSPG2:heparan sulfate proteoglycan 2 [Gene - OMIM - HGNC]
LDLRAD2:low density lipoprotein receptor class A domain containing 2 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.12
Genomic location:
Preferred name:
NM_005529.7(HSPG2):c.13033G>A (p.Gly4345Arg)
HGVS:
  • NC_000001.11:g.21823459C>T
  • NG_016740.1:g.118799G>A
  • NM_001013693.3:c.*1244C>TMANE SELECT
  • NM_001291860.2:c.13036G>A
  • NM_005529.7:c.13033G>AMANE SELECT
  • NP_001278789.1:p.Gly4346Arg
  • NP_005520.4:p.Gly4345Arg
  • NC_000001.10:g.22149952C>T
  • NM_005529.5:c.13033G>A
  • NM_005529.6:c.13033G>A
Protein change:
G4345R
Links:
dbSNP: rs148788926
NCBI 1000 Genomes Browser:
rs148788926
Molecular consequence:
  • NM_001013693.3:c.*1244C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001291860.2:c.13036G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005529.7:c.13033G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000613704Athena Diagnostics
criteria provided, single submitter

(Athena Diagnostics Criteria)
Likely benign
(Jul 2, 2018)
germlineclinical testing

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

SCV000855979Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Uncertain significance
(Jul 26, 2017)
germlineclinical testing

Citation Link,

SCV001495257Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Dec 31, 2023)
germlineclinical testing

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

SCV003811378Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Nov 18, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

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
See all PubMed Citations (3)

Details of each submission

From Athena Diagnostics, SCV000613704.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Eurofins Ntd Llc (ga), SCV000855979.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV001495257.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 4345 of the HSPG2 protein (p.Gly4345Arg). This variant is present in population databases (rs148788926, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 447542). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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

From Revvity Omics, Revvity, SCV003811378.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 1, 2024