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NM_003560.4(PLA2G6):c.2277-2A>C AND Infantile neuroaxonal dystrophy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 5, 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:
RCV000815114.5

Allele description

NM_003560.4(PLA2G6):c.2277-2A>C

Gene:
PLA2G6:phospholipase A2 group VI [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.1
Genomic location:
Preferred name:
NM_003560.4(PLA2G6):c.2277-2A>C
HGVS:
  • NC_000022.11:g.38112307T>G
  • NG_007094.3:g.107472A>C
  • NG_033059.2:g.3363A>C
  • NM_001004426.3:c.2115-2A>C
  • NM_001199562.3:c.2115-2A>C
  • NM_001349864.2:c.2277-2A>C
  • NM_001349865.2:c.2115-2A>C
  • NM_001349866.2:c.2115-2A>C
  • NM_001349867.2:c.1743-2A>C
  • NM_001349868.2:c.1599-2A>C
  • NM_001349869.2:c.1581-2A>C
  • NM_003560.4:c.2277-2A>CMANE SELECT
  • LRG_1015t1:c.2277-2A>C
  • LRG_1015:g.107472A>C
  • NC_000022.10:g.38508314T>G
  • NM_003560.2:c.2277-2A>C
Links:
dbSNP: rs552606315
NCBI 1000 Genomes Browser:
rs552606315
Molecular consequence:
  • NM_001004426.3:c.2115-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001199562.3:c.2115-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349864.2:c.2277-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349865.2:c.2115-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349866.2:c.2115-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349867.2:c.1743-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349868.2:c.1599-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001349869.2:c.1581-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_003560.4:c.2277-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Infantile neuroaxonal dystrophy (NBIA2A)
Synonyms:
NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A; Seitelberger disease; Infantile neuroaxonal dystrophy 1
Identifiers:
MONDO: MONDO:0024457; MedGen: C0270724; Orphanet: 35069; OMIM: 256600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000955558Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 5, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular diagnosis of infantile Neuro axonal Dystrophy by Next Generation Sequencing.

Goyal M, Bijarnia-Mahay S, Kingsmore S, Farrow E, Saunders C, Saxena R, Verma IC.

Indian J Pediatr. 2015 May;82(5):474-7. doi: 10.1007/s12098-014-1608-z. Epub 2014 Oct 29.

PubMed [citation]
PMID:
25348461
PMCID:
PMC4390426

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000955558.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 16 of the PLA2G6 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs552606315, gnomAD 0.003%). Disruption of this splice site has been observed in individuals with clinical features of PLA2G6-related conditions (PMID: 25348461; Invitae). ClinVar contains an entry for this variant (Variation ID: 504363). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

Last Updated: May 26, 2024