NM_001003800.2(BICD2):c.2058G>T (p.Lys686Asn) AND Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 25, 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:: RCV001318183.7

Allele description [Variation Report for NM_001003800.2(BICD2):c.2058G>T (p.Lys686Asn)]

NM_001003800.2(BICD2):c.2058G>T (p.Lys686Asn)

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.2058G>T (p.Lys686Asn)

HGVS:

NC_000009.12:g.92718587C>A
NG_033908.1:g.51215G>T
NM_001003800.2:c.2058G>TMANE SELECT
NM_015250.4:c.2058G>T
NP_001003800.1:p.Lys686Asn
NP_056065.1:p.Lys686Asn
NC_000009.11:g.95480869C>A

Protein change:

K686N

Links:

dbSNP: rs376312313

NCBI 1000 Genomes Browser:

rs376312313

Molecular consequence:

NM_001003800.2:c.2058G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015250.4:c.2058G>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

Recent activity

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ZNF561-AS1 ZNF561 antisense RNA 1 (head to head) [Homo sapiens]
ZNF561-AS1 ZNF561 antisense RNA 1 (head to head) [Homo sapiens]
Gene ID:284385

Gene
284385[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001508875	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 25, 2023)	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

SCV001508875

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 25, 2023)

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, SCV001508875.4

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

Description

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. 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 BICD2 protein function. ClinVar contains an entry for this variant (Variation ID: 1018827). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 686 of the BICD2 protein (p.Lys686Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with BICD2-related conditions (Invitae). In at least one individual the variant was observed to be de novo.

#	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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