NC_000001.11:g.228149860A>G AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 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:: RCV000633051.14

Allele description [Variation Report for NC_000001.11:g.228149860A>G]

NC_000001.11:g.228149860A>G

Gene:

GJC2:gap junction protein gamma 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.13

Genomic location:

Preferred name:

NC_000001.11:g.228149860A>G

Other names:

167G>A; -7899A>G

HGVS:

NC_000001.11:g.228149860A>G
NG_011838.1:g.5009A>G
NM_020435.3:c.-167A>G
NC_000001.10:g.228337561A>G

Note:

NCBI staff reviewed the sequence information reported in PubMed 20695017 Fig. 2C to determine the location of this variant on the current reference sequence.

Nucleotide change:

-167A-G

Links:

OMIM: 608803.0011; dbSNP: rs587776888

NCBI 1000 Genomes Browser:

rs587776888

Condition(s)

Name:: Spastic paraplegia
Identifiers:: MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000754263	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 24374284, 20695017, 21246605, 21959080, 23142375, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754263

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 2022)

germline

clinical testing

PubMed (6)
[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

GJC2 promoter mutations causing Pelizaeus-Merzbacher-like disease.

Gotoh L, Inoue K, Helman G, Mora S, Maski K, Soul JS, Bloom M, Evans SH, Goto YI, Caldovic L, Hobson GM, Vanderver A.

Mol Genet Metab. 2014 Mar;111(3):393-398. doi: 10.1016/j.ymgme.2013.12.001. Epub 2013 Dec 16. Erratum in: Mol Genet Metab. 2016 Nov;119(3):293. doi: 10.1016/j.ymgme.2016.06.011.

PubMed [citation]

PMID:: 24374284
PMCID:: PMC4183365

Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease.

Osaka H, Hamanoue H, Yamamoto R, Nezu A, Sasaki M, Saitsu H, Kurosawa K, Shimbo H, Matsumoto N, Inoue K.

Ann Neurol. 2010 Aug;68(2):250-4. doi: 10.1002/ana.22022.

PubMed [citation]

PMID:: 20695017

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754263.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects GJC2 function (PMID: 20695017, 21246605, 24374284). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 30759). This variant has been observed in individual(s) with Pelizaeus‚ÄìMerzbacher-like disease (PMID: 20695017, 21246605, 21959080, 23142375). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the GJC2 gene. It does not change the encoded amino acid sequence of the GJC2 protein.

#	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: Nov 24, 2024

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