U.S. flag

An official website of the United States government

NM_016038.4(SBDS):c.258+2T>C AND multiple conditions

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Aug 23, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000763594.9

Allele description [Variation Report for NM_016038.4(SBDS):c.258+2T>C]

NM_016038.4(SBDS):c.258+2T>C

Gene:
SBDS:SBDS ribosome maturation factor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q11.21
Genomic location:
Preferred name:
NM_016038.4(SBDS):c.258+2T>C
Other names:
c.258+2T>C
HGVS:
  • NC_000007.14:g.66994210A>G
  • NG_007277.1:g.6392T>C
  • NG_033069.1:g.2406A>G
  • NM_016038.4:c.258+2T>CMANE SELECT
  • LRG_104t1:c.258+2T>C
  • LRG_104:g.6392T>C
  • NC_000007.13:g.66459197A>G
  • NM_016038.2:c.258+2T>C
  • NM_016038.2:c.[258+2T>C]
  • NM_016038.3:c.258+2T>C
Nucleotide change:
IVS2DS, T-C, +2
Links:
OMIM: 607444.0002; dbSNP: rs113993993
NCBI 1000 Genomes Browser:
rs113993993
Molecular consequence:
  • NM_016038.4:c.258+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
Functional consequence:
effect on RNA splicing [Variation Ontology: 0362]

Condition(s)

Name:
Shwachman-Diamond syndrome 1 (SDS1)
Identifiers:
MONDO: MONDO:0044204; MedGen: C4692625; OMIM: 260400
Name:
Aplastic anemia
Identifiers:
MONDO: MONDO:0015909; MedGen: C0002874; Orphanet: 88; OMIM: 609135; Human Phenotype Ontology: HP:0001915

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000894438Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Apr 26, 2022) 		unknownclinical testing

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

SCV000898941Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 23, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753
PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]
PMCID:
PMC4544753
PMID:
25741868
DOI:
10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000894438.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000898941.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

SBDS NM_016038.3 exon 2 c.258+2T>C: This variant has been reported in the literature in several individuals with Shwachman-Diamond syndrome as homozygous or compound heterozygous (most often found in trans with c.183_184delinsCT) and is one of the most common pathogenic variants for this gene (Boocock 2003 PMID:12496757, Nakashima 2004 PMID:14749921, Austin 2005 PMID:15860664, Andolina 2013 PMID:22935661, Myers 2014 PMID:20301722). This variant is present in 0.3% (468/126574) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs113993993). This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:3196). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. In addition, functional studies have shown a deleterious effect of this variant (Orelio 2011 PMID:21695142). Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function has been reported as a disease mechanism for this gene and disease (Woloszynek 2004 PMID:15284109). In summary, this variant is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024