NM_001122955.4(BSCL2):c.844G>A (p.Ala282Thr) AND Charcot-Marie-Tooth disease type 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 20, 2024
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:: RCV000554606.8

Allele description

NM_001122955.4(BSCL2):c.844G>A (p.Ala282Thr)

Genes:

BSCL2:BSCL2 lipid droplet biogenesis associated, seipin [Gene - OMIM - HGNC]
HNRNPUL2-BSCL2:HNRNPUL2-BSCL2 readthrough (NMD candidate) [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.3

Genomic location:

Preferred name:

NM_001122955.4(BSCL2):c.844G>A (p.Ala282Thr)

HGVS:

NC_000011.10:g.62692395C>T
NG_008461.1:g.22180G>A
NG_033077.1:g.2505G>A
NM_001122955.4:c.844G>AMANE SELECT
NM_001130702.2:c.652G>A
NM_001386027.1:c.844G>A
NM_001386028.1:c.844G>A
NM_032667.6:c.652G>A
NP_001116427.1:p.Ala282Thr
NP_001124174.2:p.Ala218Thr
NP_001372956.1:p.Ala282Thr
NP_001372957.1:p.Ala282Thr
NP_116056.3:p.Ala218Thr
LRG_235t2:c.652G>A
LRG_235:g.22180G>A
LRG_235p2:p.Ala218Thr
NC_000011.9:g.62459867C>T
NR_037946.1:n.3364G>A

Protein change:

A218T

Links:

dbSNP: rs190842600

NCBI 1000 Genomes Browser:

rs190842600

Molecular consequence:

NM_001122955.4:c.844G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130702.2:c.652G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001386027.1:c.844G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001386028.1:c.844G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032667.6:c.652G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_037946.1:n.3364G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000657780	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 20, 2024)	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

SCV000657780

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 20, 2024)

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, SCV000657780.6

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 218 of the BSCL2 protein (p.Ala218Thr). This variant is present in population databases (rs190842600, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 476815). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BSCL2 protein function with a positive predictive value of 80%. 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: Aug 18, 2024

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