NM_005529.7(HSPG2):c.6748G>T (p.Glu2250Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 2, 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:: RCV003721416.2

Allele description [Variation Report for NM_005529.7(HSPG2):c.6748G>T (p.Glu2250Ter)]

NM_005529.7(HSPG2):c.6748G>T (p.Glu2250Ter)

Genes:

LOC126805655:CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:22178409-22179608 [Gene]
HSPG2:heparan sulfate proteoglycan 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.12

Genomic location:

Preferred name:

NM_005529.7(HSPG2):c.6748G>T (p.Glu2250Ter)

HGVS:

NC_000001.11:g.21852210C>A
NG_016740.1:g.90048G>T
NG_081979.1:g.395C>A
NM_001291860.2:c.6751G>T
NM_005529.7:c.6748G>TMANE SELECT
NP_001278789.1:p.Glu2251Ter
NP_005520.4:p.Glu2250Ter
NC_000001.10:g.22178703C>A

Protein change:

E2250*

Molecular consequence:

NM_001291860.2:c.6751G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005529.7:c.6748G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Homo sapiens ALG14 UDP-N-acetylglucosaminyltransferase subunit (ALG14...
PREDICTED: Homo sapiens ALG14 UDP-N-acetylglucosaminyltransferase subunit (ALG14), transcript variant X1, mRNA
gi|2217264734|ref|XM_005270582.5|

Nucleotide
hypothetical protein [Escherichia coli]
hypothetical protein [Escherichia coli]
gi|506593518|ref|WP_016059017.1|

Protein
Microbe sample from Streptococcus suis
Microbe sample from Streptococcus suis

biosample
uncharacterized protein AT3G44763 [Arabidopsis thaliana]
uncharacterized protein AT3G44763 [Arabidopsis thaliana]
gi|1162502435|ref|NP_001336524.1|

Protein
recombination activating protein 2, partial [Vansonia rueppellii]
recombination activating protein 2, partial [Vansonia rueppellii]
gi|397713662|gb|AFO60431.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004505610	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 2, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11279527, 16927315, 20542149, 23836246, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004505610

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 2, 2023)

germline

clinical testing

PubMed (5)
[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

Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene.

Arikawa-Hirasawa E, Wilcox WR, Le AH, Silverman N, Govindraj P, Hassell JR, Yamada Y.

Nat Genet. 2001 Apr;27(4):431-4.

PubMed [citation]

PMID:: 11279527

Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome.

Stum M, Davoine CS, Vicart S, Guillot-Noël L, Topaloglu H, Carod-Artal FJ, Kayserili H, Hentati F, Merlini L, Urtizberea JA, Hammouda el-H, Quan PC, Fontaine B, Nicole S.

Hum Mutat. 2006 Nov;27(11):1082-91.

PubMed [citation]

PMID:: 16927315

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004505610.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Glu2250*) in the HSPG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSPG2 are known to be pathogenic (PMID: 11279527, 16927315, 20542149, 23836246). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HSPG2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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