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NM_001122955.4(BSCL2):c.455A>G (p.Asn152Ser) AND Charcot-Marie-Tooth disease type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 14, 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:
RCV000168078.19

Allele description [Variation Report for NM_001122955.4(BSCL2):c.455A>G (p.Asn152Ser)]

NM_001122955.4(BSCL2):c.455A>G (p.Asn152Ser)

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.455A>G (p.Asn152Ser)
Other names:
NM_001122955.3(BSCL2):c.455A>G(p.Asn152Ser); NM_001130702.2(BSCL2):c.263A>G(p.Asn88Ser); NM_032667.6(BSCL2):c.263A>G(p.Asn88Ser)
HGVS:
  • NC_000011.10:g.62702499T>C
  • NG_008461.1:g.12076A>G
  • NM_001122955.4:c.455A>GMANE SELECT
  • NM_001130702.2:c.263A>G
  • NM_001386027.1:c.455A>G
  • NM_001386028.1:c.455A>G
  • NM_032667.6:c.263A>G
  • NP_001116427.1:p.Asn152Ser
  • NP_001116427.1:p.Asn152Ser
  • NP_001124174.2:p.Asn88Ser
  • NP_001372956.1:p.Asn152Ser
  • NP_001372957.1:p.Asn152Ser
  • NP_116056.3:p.Asn88Ser
  • LRG_235t1:c.455A>G
  • LRG_235t2:c.263A>G
  • LRG_235:g.12076A>G
  • LRG_235p1:p.Asn152Ser
  • LRG_235p2:p.Asn88Ser
  • NC_000011.9:g.62469971T>C
  • NM_001122955.2:c.455A>G
  • NM_001122955.3:c.455A>G
  • NM_001122955.4:c.455A>G
  • NM_032667.5:c.263A>G
  • NR_037946.1:n.2975A>G
  • Q96G97:p.Asn88Ser
Protein change:
N152S; ASN88SER
Links:
UniProtKB: Q96G97#VAR_022375; OMIM: 606158.0013; dbSNP: rs137852972
NCBI 1000 Genomes Browser:
rs137852972
Molecular consequence:
  • NM_001122955.4:c.455A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001130702.2:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386027.1:c.455A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386028.1:c.455A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032667.6:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_037946.1:n.2975A>G - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000218732Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 14, 2023) 		germlineclinical testing

PubMed (13)
[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

Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation.

Auer-Grumbach M, Schlotter-Weigel B, Lochmüller H, Strobl-Wildemann G, Auer-Grumbach P, Fischer R, Offenbacher H, Zwick EB, Robl T, Hartl G, Hartung HP, Wagner K, Windpassinger C; Austrian Peripheral Neuropathy Study Group..

Ann Neurol. 2005 Mar;57(3):415-24.

PubMed [citation]
PMID:
15732094

BSCL2 mutations in two Dutch families with overlapping Silver syndrome-distal hereditary motor neuropathy.

van de Warrenburg BP, Scheffer H, van Eijk JJ, Versteeg MH, Kremer H, Zwarts MJ, Schelhaas HJ, van Engelen BG.

Neuromuscul Disord. 2006 Feb;16(2):122-5. Epub 2006 Jan 19.

PubMed [citation]
PMID:
16427281
See all PubMed Citations (13)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000218732.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 88 of the BSCL2 protein (p.Asn88Ser). This variant is present in population databases (rs137852972, gnomAD 0.01%). This missense change has been observed in individuals with autosomal dominant BSCL2-related conditions (PMID: 14981520, 15732094, 16427281, 20598714, 23553728, 25219579, 25454168). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4543). 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%. Experimental studies have shown that this missense change affects BSCL2 function (PMID: 14981520, 17387721, 18585921, 21957196, 22045697, 24345054). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024