NM_001003800.2(BICD2):c.1997A>C (p.Asp666Ala) AND Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2021
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:: RCV000796773.5

Allele description [Variation Report for NM_001003800.2(BICD2):c.1997A>C (p.Asp666Ala)]

NM_001003800.2(BICD2):c.1997A>C (p.Asp666Ala)

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.1997A>C (p.Asp666Ala)

HGVS:

NC_000009.12:g.92718648T>G
NG_033908.1:g.51154A>C
NM_001003800.2:c.1997A>CMANE SELECT
NM_015250.4:c.1997A>C
NP_001003800.1:p.Asp666Ala
NP_056065.1:p.Asp666Ala
NC_000009.11:g.95480930T>G
NM_001003800.1:c.1997A>C

Protein change:

D666A

Links:

dbSNP: rs1587668190

NCBI 1000 Genomes Browser:

rs1587668190

Molecular consequence:

NM_001003800.2:c.1997A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015250.4:c.1997A>C - 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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Related Structures (List) for Protein (Select 284832607) (59)
Structure
Danio rerio strain:Tuebingen
Danio rerio strain:Tuebingen
Zebrafish reference genome sequence

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BioProject Links for Protein (Select 67459920) (1)
BioProject
Homo sapiens kinesin family member 22 (KIF22), transcript variant 1, mRNA
Homo sapiens kinesin family member 22 (KIF22), transcript variant 1, mRNA
gi|372266144|ref|NM_007317.2|

Nucleotide
PMC Links for GEO Profiles (Select 45807402) (62)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000936300	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2021)	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

SCV000936300

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2021)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000936300.4

#	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 aspartic acid with alanine at codon 666 of the BICD2 protein (p.Asp666Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with BICD2-related conditions.

#	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: Sep 29, 2024

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