NM_020376.4(PNPLA2):c.1243_1245delinsCAG (p.Tyr415Gln) AND Neutral lipid storage myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 8, 2016
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:: RCV000554760.3

Allele description [Variation Report for NM_020376.4(PNPLA2):c.1243_1245delinsCAG (p.Tyr415Gln)]

NM_020376.4(PNPLA2):c.1243_1245delinsCAG (p.Tyr415Gln)

Gene:

PNPLA2:patatin like phospholipase domain containing 2 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_020376.4(PNPLA2):c.1243_1245delinsCAG (p.Tyr415Gln)

HGVS:

NC_000011.10:g.824590_824592delinsCAG
NG_023394.1:g.10690_10692delinsCAG
NM_020376.4:c.1243_1245delinsCAGMANE SELECT
NP_065109.1:p.Tyr415Gln
NC_000011.9:g.824590_824592delinsCAG

Protein change:

Y415Q

Links:

dbSNP: rs1554976791

NCBI 1000 Genomes Browser:

rs1554976791

Molecular consequence:

NM_020376.4:c.1243_1245delinsCAG - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neutral lipid storage myopathy (NLSDM)
Synonyms:: Neutral lipid storage disease with myopathy; Neutral lipid storage disease without ichthyosis
Identifiers:: MONDO: MONDO:0012545; MedGen: C1853136; Orphanet: 98908; OMIM: 610717

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000641118	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 8, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000641118

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 8, 2016)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000641118.3

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

Description

In summary, this variant is a novel missense change with uncertain impact on mRNA splicing and protein function. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PNPLA2-related disease. This sequence change replaces tyrosine with glutamine at codon 415 of the PNPLA2 protein (p.Tyr415Gln). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and glutamine. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies.

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine