NM_004766.3(COPB2):c.1237_1238del (p.Lys413fs) AND Osteoporosis, childhood- or juvenile-onset, with developmental delay

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 24, 2022
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV002246506.1

Allele description [Variation Report for NM_004766.3(COPB2):c.1237_1238del (p.Lys413fs)]

NM_004766.3(COPB2):c.1237_1238del (p.Lys413fs)

Gene:

COPB2:COPI coat complex subunit beta 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q23

Genomic location:

Preferred name:

NM_004766.3(COPB2):c.1237_1238del (p.Lys413fs)

Other names:

p.K413NfsTer3

HGVS:

NC_000003.12:g.139369513_139369514del
NM_004766.3:c.1237_1238delMANE SELECT
NP_004757.1:p.Lys413fs
NC_000003.11:g.139088355_139088356del
NM_004766.2:c.1237_1238delAA
NR_023350.1:n.1446_1447del

Protein change:

K413fs

Links:

OMIM: 606990.0002; dbSNP: rs2107801839

Molecular consequence:

NM_004766.3:c.1237_1238del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_023350.1:n.1446_1447del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Osteoporosis, childhood- or juvenile-onset, with developmental delay
Identifiers:: MONDO: MONDO:0859253; MedGen: C5676992; OMIM: 619884

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002520540	OMIM	no assertion criteria provided	Pathogenic (May 24, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520540

OMIM

no assertion criteria provided

Pathogenic
(May 24, 2022)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay.

Marom R, Burrage LC, Venditti R, Clément A, Blanco-Sánchez B, Jain M, Scott DA, Rosenfeld JA, Sutton VR, Shinawi M, Mirzaa G, DeVile C, Roberts R, Calder AD, Allgrove J, Grafe I, Lanza DG, Li X, Joeng KS, Lee YC, Song IW, Sliepka JM, et al.

Am J Hum Genet. 2021 Sep 2;108(9):1710-1724. doi: 10.1016/j.ajhg.2021.08.002. Epub 2021 Aug 26.

PubMed [citation]

PMID:: 34450031
PMCID:: PMC8456174

Details of each submission

From OMIM, SCV002520540.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 9-year-old girl of Caucasian and Native American ancestry (patient 1) with multiple fractures, low bone mineral density, and speech delay with learning disabilities (OPDD; 619884), Marom et al. (2021) identified heterozygosity for a de novo 2-bp deletion (c.1237_1238delAA, NM_004766.2) in the COPB2 gene, causing a frameshift predicted to result in a premature termination codon (Lys413AspfsTer3). Sanger sequencing of DNA from the proband and her parents confirmed the de novo origin of the variant, which was not found in the gnomAD database. Sequencing of mRNA on whole blood from the proband demonstrated that the variant results in nonsense-mediated decay; RT-qPCR in patient lymphoblastoid cells supported this finding by showing an approximately 50% reduction in COPB2 expression compared to parents and unaffected sib.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 13, 2025

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