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NM_001003800.2(BICD2):c.1667A>G (p.Tyr556Cys) AND Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 16, 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:
RCV001069097.2

Allele description

NM_001003800.2(BICD2):c.1667A>G (p.Tyr556Cys)

Gene:
BICD2:BICD cargo adaptor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.31
Genomic location:
Preferred name:
NM_001003800.2(BICD2):c.1667A>G (p.Tyr556Cys)
HGVS:
  • NC_000009.12:g.92718978T>C
  • NG_033908.1:g.50824A>G
  • NM_001003800.2:c.1667A>GMANE SELECT
  • NM_015250.4:c.1667A>G
  • NP_001003800.1:p.Tyr556Cys
  • NP_056065.1:p.Tyr556Cys
  • NC_000009.11:g.95481260T>C
  • NC_000009.11:g.95481260T>C
  • NM_001003800.1:c.1667A>G
Protein change:
Y556C
Links:
dbSNP: rs1587668748
NCBI 1000 Genomes Browser:
rs1587668748
Molecular consequence:
  • NM_001003800.2:c.1667A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015250.4:c.1667A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (SMALED2A)
Synonyms:
SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, 2A, CHILDHOOD ONSET, AUTOSOMAL DOMINANT; Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant
Identifiers:
MONDO: MONDO:0014121; MedGen: C4747715; Orphanet: 363447; Orphanet: 363454; OMIM: 615290

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001234243Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 16, 2023) 		germlineclinical testing

PubMed (2)
[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

Novel BICD2 mutation in a Japanese family with autosomal dominant lower extremity-predominant spinal muscular atrophy-2.

Yoshioka M, Morisada N, Toyoshima D, Yoshimura H, Nishio H, Iijima K, Takeshima Y, Uehara T, Kosaki K.

Brain Dev. 2018 Apr;40(4):343-347. doi: 10.1016/j.braindev.2017.12.001. Epub 2017 Dec 19.

PubMed [citation]
PMID:
29273277

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, SCV001234243.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 862389). 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 not expected to disrupt BICD2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 556 of the BICD2 protein (p.Tyr556Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BICD2-related conditions (PMID: 29273277; Invitae). In at least one individual the variant was observed to be de novo.

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

Last Updated: Feb 28, 2024