NM_006363.6(SEC23B):c.1588C>T (p.Arg530Trp) AND Congenital dyserythropoietic anemia, type II

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 11, 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:: RCV000001283.5

Allele description [Variation Report for NM_006363.6(SEC23B):c.1588C>T (p.Arg530Trp)]

NM_006363.6(SEC23B):c.1588C>T (p.Arg530Trp)

Gene:

SEC23B:SEC23 homolog B, COPII coat complex component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20p11.23

Genomic location:

Preferred name:

NM_006363.6(SEC23B):c.1588C>T (p.Arg530Trp)

HGVS:

NC_000020.11:g.18543095C>T
NG_016281.2:g.40614C>T
NM_001172745.3:c.1588C>T
NM_001172746.3:c.1534C>T
NM_006363.4:c.1588C>T
NM_006363.6:c.1588C>TMANE SELECT
NM_032985.6:c.1588C>T
NM_032986.5:c.1588C>T
NP_001166216.1:p.Arg530Trp
NP_001166217.1:p.Arg512Trp
NP_006354.2:p.Arg530Trp
NP_116780.1:p.Arg530Trp
NP_116781.1:p.Arg530Trp
LRG_1134t1:c.1588C>T
LRG_1134:g.40614C>T
LRG_1134p1:p.Arg530Trp
NC_000020.10:g.18523739C>T
NM_001172745.2:c.1588C>T
Q15437:p.Arg530Trp

Protein change:

R512W; ARG530TRP

Links:

UniProtKB: Q15437#VAR_062307; OMIM: 610512.0003; dbSNP: rs121918223

NCBI 1000 Genomes Browser:

rs121918223

Molecular consequence:

NM_001172745.3:c.1588C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001172746.3:c.1534C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006363.6:c.1588C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032985.6:c.1588C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032986.5:c.1588C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital dyserythropoietic anemia, type II (CDAN2)
Synonyms:: Dyserythropoietic anemia, congenital type 2; CDA 2; HEMPAS anemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009134; MedGen: C1306589; Orphanet: 98873; OMIM: 224100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021433	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2009)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004039080	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19561605, 24724984 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000021433

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2009)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004039080

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Aug 11, 2023)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II.

Schwarz K, Iolascon A, Verissimo F, Trede NS, Horsley W, Chen W, Paw BH, Hopfner KP, Holzmann K, Russo R, Esposito MR, Spano D, De Falco L, Heinrich K, Joggerst B, Rojewski MT, Perrotta S, Denecke J, Pannicke U, Delaunay J, Pepperkok R, Heimpel H.

Nat Genet. 2009 Aug;41(8):936-40. doi: 10.1038/ng.405. Epub 2009 Jun 28.

PubMed [citation]

PMID:: 19561605

Successful hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia type II.

Unal S, Russo R, Gumruk F, Kuskonmaz B, Cetin M, Sayli T, Tavil B, Langella C, Iolascon A, Uckan Cetinkaya D.

Pediatr Transplant. 2014 Jun;18(4):E130-3. doi: 10.1111/petr.12254. Epub 2014 Apr 12.

PubMed [citation]

PMID:: 24724984

Details of each submission

From OMIM, SCV000021433.3

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

Description

For discussion of the arg530-to-trp (R530W) mutation in the SEC23B gene that was found in compound heterozygous state in patients with congenital dyserythropoietic anemia type II (CDAN2; 224100) by Schwarz et al. (2009), see 610512.0002.

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004039080.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: SEC23B c.1588C>T (p.Arg530Trp) results in a non-conservative amino acid change located in the Sec23/Sec24, helical domain (IPR006900) of the encoded protein sequence. This alters a highly conserved residue in which another missense variant p.Arg530Gln) has been found in association with disease (HGMD). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251468 control chromosomes (gnomAD). c.1588C>T has been reported in the literature in individuals affected with Congenital dyserythropoietic anemia, type II who were reported as compound heterozygous with other pathogenic variants (Schwarz_2009, Unal_2014). These data indicate that the variant is likely to be associated with disease. 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: 19561605, 24724984). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Mar 5, 2024

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