NM_006363.6(SEC23B):c.1385A>G (p.Tyr462Cys) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 29, 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:: RCV003772156.1

Allele description [Variation Report for NM_006363.6(SEC23B):c.1385A>G (p.Tyr462Cys)]

NM_006363.6(SEC23B):c.1385A>G (p.Tyr462Cys)

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.1385A>G (p.Tyr462Cys)

HGVS:

NC_000020.11:g.18535723A>G
NG_016281.2:g.33242A>G
NM_001172745.3:c.1385A>G
NM_001172746.3:c.1331A>G
NM_006363.6:c.1385A>GMANE SELECT
NM_032985.6:c.1385A>G
NM_032986.5:c.1385A>G
NP_001166216.1:p.Tyr462Cys
NP_001166217.1:p.Tyr444Cys
NP_006354.2:p.Tyr462Cys
NP_116780.1:p.Tyr462Cys
NP_116781.1:p.Tyr462Cys
LRG_1134t1:c.1385A>G
LRG_1134:g.33242A>G
LRG_1134p1:p.Tyr462Cys
NC_000020.10:g.18516367A>G
NM_006363.4:c.[1385A>G]

Protein change:

Y444C

Links:

dbSNP: rs780978419

NCBI 1000 Genomes Browser:

rs780978419

Molecular consequence:

NM_001172745.3:c.1385A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001172746.3:c.1331A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006363.6:c.1385A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032985.6:c.1385A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032986.5:c.1385A>G - 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

Name:: Cowden syndrome 7 (CWS7)
Identifiers:: MONDO: MONDO:0014802; MedGen: C4225179; Orphanet: 201; OMIM: 616858

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004571386	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19561605, 24801240, 25044164, 25418799, 28879554, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004571386

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 29, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

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

Congenital dyserythropoietic anemia, type II with SEC23B exon 12 c.1385 A → G mutation, and pseudo-Gaucher cells in two siblings.

Sharma P, Das R, Bansal D, Trehan A.

Hematology. 2015 Mar;20(2):104-7. doi: 10.1179/1607845414Y.0000000166. Epub 2014 May 6.

PubMed [citation]

PMID:: 24801240

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004571386.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 462 of the SEC23B protein (p.Tyr462Cys). This variant is present in population databases (rs780978419, gnomAD 0.02%). This missense change has been observed in individuals with congenital dyserythropoietic anemia type II (PMID: 19561605, 24801240, 25044164, 25418799, 28879554). ClinVar contains an entry for this variant (Variation ID: 1325043). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SEC23B protein function. 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.

#	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: May 12, 2024

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