NM_016038.4(SBDS):c.183_184delinsCT (p.Lys62Ter) AND Shwachman syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 16, 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:: RCV004017224.1

Allele description [Variation Report for NM_016038.4(SBDS):c.183_184delinsCT (p.Lys62Ter)]

NM_016038.4(SBDS):c.183_184delinsCT (p.Lys62Ter)

Gene:

SBDS:SBDS ribosome maturation factor [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_016038.4(SBDS):c.183_184delinsCT (p.Lys62Ter)

HGVS:

NC_000007.14:g.66994286_66994287delinsAG
NG_033069.1:g.2482_2483delinsAG
NM_016038.4:c.183_184delinsCTMANE SELECT
NP_057122.2:p.Lys62Ter
NP_057122.2:p.Lys62Ter
LRG_104t1:c.183_184delTAinsCT
LRG_104:g.6315_6316delinsCT
LRG_104p1:p.Lys62Ter
NC_000007.13:g.66459273_66459274delinsAG
NM_016038.2:c.183_184delTAinsCT
NM_016038.3:c.183_184delinsCT
NM_016038.4:c.183_184delTAinsCTMANE SELECT
p.Lys62*
p.Lys62X

Protein change:

K62*; LYS62TER

Links:

OMIM: 607444.0001; dbSNP: rs113993991

NCBI 1000 Genomes Browser:

rs113993991

Molecular consequence:

NM_016038.4:c.183_184delinsCT - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

effect on RNA splicing [Variation Ontology: 0362]

Condition(s)

Name:: Shwachman syndrome
Synonyms:: Pancreatic insufficiency and bone marrow dysfunction; Shwachman-Bodian syndrome; Lipomatosis of pancreas, congenital; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009833; MedGen: C0272170; Orphanet: 811; OMIM: PS260400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967682	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 16, 2024)	germline	clinical testing	PubMed (16) [See all records that cite these PMIDs] 29375851, 12496757, 15342903, 14749921, 15860664, 15701631, 21695142, 22934832, 22935661, 24388329, 24629175, 25729736, 25844324, 26081292, 29753700, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967682

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 16, 2024)

germline

clinical testing

PubMed (16)
[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

Association of isochromosome (7)(q10) in Shwachman-Diamond syndrome with the severity of cytopenia.

Shimosato Y, Tanoshima R, Tsujimoto SI, Takeuchi M, Sasaki K, Kajiwara R, Goto H, Nagai J, Yanagimachi MD, Ito S, Yokota S.

Clin Case Rep. 2018 Jan;6(1):125-128. doi: 10.1002/ccr3.1249.

PubMed [citation]

PMID:: 29375851
PMCID:: PMC5771925

Mutations in SBDS are associated with Shwachman-Diamond syndrome.

Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM.

Nat Genet. 2003 Jan;33(1):97-101. Epub 2002 Dec 23.

PubMed [citation]

PMID:: 12496757

See all PubMed Citations (16)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967682.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

The p.Lys62X variant in SBDS is the most common pathogenic variant identified in individuals with Shwachman-Diamond syndrome (Boocock 2003 PMID: 12496757). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID: 3195) and has been identified in 0.1% (69/59956) of Admixed American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0); however, this allele frequency may not be accurate due to the presence of a pseudogene (SBDSP). Note that this variant was documented separately as chr7:66994286T>A and chr7:66994287A>G in gnomAD. This variant usually occurs as the result of a gene conversion event and results in the introduction of a premature termination codon at position 62. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the SBDS gene is an established disease mechanism in Shwachman-Diamond syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Shwachman-Diamond syndrome. ACMG/AMP criteria applied: PVS1, PM3_Very Strong.

#	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: Nov 30, 2024

ClinVar

Relating variation to medicine