NM_001003800.2(BICD2):c.2100C>A (p.Asn700Lys) AND Spinal muscular atrophy with lower extremity predominance

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 4, 2024
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:: RCV004526518.2

Allele description [Variation Report for NM_001003800.2(BICD2):c.2100C>A (p.Asn700Lys)]

NM_001003800.2(BICD2):c.2100C>A (p.Asn700Lys)

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.2100C>A (p.Asn700Lys)

HGVS:

NC_000009.12:g.92718545G>T
NG_033908.1:g.51257C>A
NM_001003800.2:c.2100C>AMANE SELECT
NM_015250.4:c.2100C>A
NP_001003800.1:p.Asn700Lys
NP_056065.1:p.Asn700Lys
NC_000009.11:g.95480827G>T

Protein change:

N700K

Molecular consequence:

NM_001003800.2:c.2100C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015250.4:c.2100C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spinal muscular atrophy with lower extremity predominance
Synonyms:: Autosomal dominant childhood-onset proximal spinal muscular atrophy
Identifiers:: MONDO: MONDO:0018190; MedGen: C1834690; OMIM: PS158600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005040423	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 4, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 35627109, 29274205, 33547725 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005040423

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 4, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience.

Kucińska-Chahwan A, Geremek M, Roszkowski T, Bijok J, Massalska D, Ciebiera M, Correia H, Pereira-Caetano I, Barreta A, Obersztyn E, Kutkowska-Kaźmierczak A, Własienko P, Krajewska-Walasek M, Węgrzyn P, Dudarewicz L, Krzeszowski W, Rybak-Krzyszkowska M, Nowakowska B.

Genes (Basel). 2022 Apr 21;13(5). doi:pii: 724. 10.3390/genes13050724.

PubMed [citation]

PMID:: 35627109
PMCID:: PMC9140952

Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.

Ahmed AA, Skaria P, Safina NP, Thiffault I, Kats A, Taboada E, Habeebu S, Saunders C.

Am J Med Genet A. 2018 Feb;176(2):359-367. doi: 10.1002/ajmg.a.38577. Epub 2017 Dec 23.

PubMed [citation]

PMID:: 29274205

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040423.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: BICD2 c.2100C>A (p.Asn700Lys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 247344 control chromosomes. c.2100C>A has been reported in the literature as de novo in a fetus affected with Spinal Muscular Atrophy With Lower Extremity Predominance. Additionally, another variant resulting in the same amino acid change c.2100C>G (p.Asn700Lys) was also observed as de novo in an affected fetus (Ahmed_2018) and classified as pathogenic in ClinVar. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35627109, 33547725, 29274205). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Jul 7, 2024

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