NM_003560.4(PLA2G6):c.1506G>C (p.Lys502Asn) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 26, 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:: RCV003403171.1

Allele description [Variation Report for NM_003560.4(PLA2G6):c.1506G>C (p.Lys502Asn)]

NM_003560.4(PLA2G6):c.1506G>C (p.Lys502Asn)

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.1506G>C (p.Lys502Asn)

HGVS:

NC_000022.11:g.38123180C>G
NG_007094.3:g.96599G>C
NM_001004426.3:c.1344G>C
NM_001199562.3:c.1344G>C
NM_001349864.2:c.1506G>C
NM_001349865.2:c.1344G>C
NM_001349866.2:c.1344G>C
NM_001349867.2:c.972G>C
NM_001349868.2:c.828G>C
NM_001349869.2:c.810G>C
NM_003560.4:c.1506G>CMANE SELECT
NP_001004426.1:p.Lys448Asn
NP_001186491.1:p.Lys448Asn
NP_001336793.1:p.Lys502Asn
NP_001336794.1:p.Lys448Asn
NP_001336795.1:p.Lys448Asn
NP_001336796.1:p.Lys324Asn
NP_001336797.1:p.Lys276Asn
NP_001336798.1:p.Lys270Asn
NP_003551.2:p.Lys502Asn
LRG_1015t1:c.1506G>C
LRG_1015:g.96599G>C
LRG_1015p1:p.Lys502Asn
NC_000022.10:g.38519187C>G
NG_007094.2:g.87511G>C
NM_003560.2:c.1506G>C

Protein change:

K270N

Links:

dbSNP: rs1555988382

NCBI 1000 Genomes Browser:

rs1555988382

Molecular consequence:

NM_001004426.3:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.1506G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.972G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.828G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.810G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.1506G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004122199	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29915382, 16783378, 18799783 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004122199

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 26, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes.

Sun M, Johnson AK, Nelakuditi V, Guidugli L, Fischer D, Arndt K, Ma L, Sandford E, Shakkottai V, Boycott K, Warman-Chardon J, Li Z, Del Gaudio D, Burmeister M, Gomez CM, Waggoner DJ, Das S.

Genet Med. 2019 Jan;21(1):195-206. doi: 10.1038/s41436-018-0007-7. Epub 2018 Jun 18.

PubMed [citation]

PMID:: 29915382
PMCID:: PMC6524765

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.

Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, Cangul H, Coryell J, Canham N, Nardocci N, Zorzi G, Pasha S, Rodriguez D, Desguerre I, Mubaidin A, Bertini E, Trembath RC, Simonati A, Schanen C, Johnson CA, Levinson B, Woods CG, et al.

Nat Genet. 2006 Jul;38(7):752-4. Epub 2006 Jun 18. Erratum in: Nat Genet. 2006 Aug;38(8):957.

PubMed [citation]

PMID:: 16783378
PMCID:: PMC2117328

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004122199.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: PLA2G6 c.1506G>C (p.Lys502Asn) results in a non-conservative amino acid change located in the patatin-like phospholipase domain (IPR002641) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 158944 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1506G>C has been reported in the literature as a compound heterozygous genotype in at least two individuals affected with classical infantile neuroaxonal dystrophy (e.g. Morgan_2006, Gregory_2008). However, it has also been reported in a child who underwent WES for an ataxia of unknown etiology who was found to have a nonsense variant in trans and an exon 3-6 deletion in cis with the variant, providing possible evidence for a benign role (Sun_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18799783, 16783378, 29915382). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: Nov 25, 2023

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