NM_001003800.2(BICD2):c.2057A>T (p.Lys686Met) AND Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 2018
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:: RCV000793566.7

Allele description [Variation Report for NM_001003800.2(BICD2):c.2057A>T (p.Lys686Met)]

NM_001003800.2(BICD2):c.2057A>T (p.Lys686Met)

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.2057A>T (p.Lys686Met)

HGVS:

NC_000009.12:g.92718588T>A
NG_033908.1:g.51214A>T
NM_001003800.2:c.2057A>TMANE SELECT
NM_015250.4:c.2057A>T
NP_001003800.1:p.Lys686Met
NP_056065.1:p.Lys686Met
NC_000009.11:g.95480870T>A
NM_001003800.1:c.2057A>T

Protein change:

K686M

Links:

dbSNP: rs1587668129

NCBI 1000 Genomes Browser:

rs1587668129

Molecular consequence:

NM_001003800.2:c.2057A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015250.4:c.2057A>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000932926	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 13, 2018)	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

SCV000932926

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 13, 2018)

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, SCV000932926.4

#	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 lysine with methionine at codon 686 of the BICD2 protein (p.Lys686Met). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BICD2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Sep 29, 2024

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