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 [Variation Report for NM_003560.4(PLA2G6):c.2277-2A>C]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000955558	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25348461, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000955558

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

PubMed (4)
[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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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: May 26, 2024

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