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NM_022041.4(GAN):c.1503-2A>G AND Giant axonal neuropathy 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 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:
RCV003226135.2

Allele description [Variation Report for NM_022041.4(GAN):c.1503-2A>G]

NM_022041.4(GAN):c.1503-2A>G

Gene:
GAN:gigaxonin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q23.2
Genomic location:
Preferred name:
NM_022041.4(GAN):c.1503-2A>G
Other names:
NM_022041.4:c.1503-2A>G
HGVS:
  • NC_000016.10:g.81377217A>G
  • NG_009007.1:g.67252A>G
  • NM_001377486.1:c.864-2A>G
  • NM_022041.4:c.1503-2A>GMANE SELECT
  • LRG_242:g.67252A>G
  • NC_000016.9:g.81410822A>G
Molecular consequence:
  • NM_001377486.1:c.864-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_022041.4:c.1503-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Giant axonal neuropathy 1 (GAN1)
Synonyms:
GIANT AXONAL NEUROPATHY 1, AUTOSOMAL RECESSIVE
Identifiers:
MONDO: MONDO:0009749; MedGen: C1850386; Orphanet: 643; OMIM: 256850

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003922323Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 2, 2023) 		germlinecuration

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003922323.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The homozygous c.1503-2A>G variant in GAN was identified by our study in one individual with global developmental delay and neurodegeneration. The c.1503-2A>G variant in GAN has not been previously reported in individuals with giant axonal neuropathy 1. This variant was absent from the large population studies. This variant is located in the 5' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. There is an in-frame cryptic splice site 108 bases from the intron-exon boundary, providing evidence that this variant may delete 36 amino acids instead of causing loss of function. However, this information is not predictive enough to determine pathogenicity. Loss of function of the GAN gene is an established disease mechanism in autosomal recessive giant axonal neuropathy 1. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting, PM3_Supporting (Richards 2015).

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

Last Updated: Mar 30, 2024