ClinVar Genomic variation as it relates to human health
NM_016038.4(SBDS):c.184A>T (p.Lys62Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_016038.4(SBDS):c.184A>T (p.Lys62Ter)
Variation ID: 449095 Accession: VCV000449095.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q11.21 7: 66994286 (GRCh38) [ NCBI UCSC ] 7: 66459273 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 19, 2017 Feb 4, 2024 Sep 12, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_016038.4:c.184A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_057122.2:p.Lys62Ter nonsense NM_016038.2:c.[184A>T] NC_000007.14:g.66994286T>A NC_000007.13:g.66459273T>A NG_007277.1:g.6316A>T NG_033069.1:g.2482T>A LRG_104:g.6316A>T LRG_104t1:c.184A>T - Protein change
- K62*
- Other names
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- Canonical SPDI
- NC_000007.14:66994285:T:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00060 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00017
Exome Aggregation Consortium (ExAC) 0.00041
1000 Genomes Project 0.00060
The Genome Aggregation Database (gnomAD) 0.00099
1000 Genomes Project 30x 0.00187
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SBDS | - | - |
GRCh38 GRCh37 |
107 | 130 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Oct 23, 2020 | RCV000523697.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2017 | RCV000626934.3 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Sep 12, 2022 | RCV000987895.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 25, 2021 | RCV001293358.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Jan 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Agenesis of permanent teeth
Deeply set eye Microcephaly Short stature Splenomegaly
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000747637.1
First in ClinVar: May 12, 2018 Last updated: May 12, 2018 |
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Pathogenic
(Jul 10, 2017)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000616861.2
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Comment:
The K62X variant in the SBDS gene has been reported previously in an individual with Shwachman-Diamond syndrome who also harbored the c.258+2 T>C variant on … (more)
The K62X variant in the SBDS gene has been reported previously in an individual with Shwachman-Diamond syndrome who also harbored the c.258+2 T>C variant on the other SBDS allele (Pronicka et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies demonstrate that the K62X variant results in abnormally low cytoplasmic protein levels and loss of protein function (Orelio et al., 2011; Shammas et al., 2005). The K62X variant is not observed in large population cohorts (Lek et al., 2016). Historically this variant as been reported as c.183_184delTAinsCT. This event is derived from a recombination event with a known psuedogene carrying this variant. (less)
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Likely pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Shwachman-Diamond syndrome 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137385.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446841.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Glutaric aciduria (present) , Failure to thrive (present) , Pulmonary arterial hypertension (present)
Sex: female
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Pathogenic
(Feb 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
paternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001481812.1
First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021 |
Comment:
The variant chr7-66459273-T-A, SBDS(NM_016038.4):c.184A>T,p.(Lys62*) was identified in an individual with NDD. Inheritance was paternal (heterozygous). The variant was reviewed according to current ACMG recommendations and … (more)
The variant chr7-66459273-T-A, SBDS(NM_016038.4):c.184A>T,p.(Lys62*) was identified in an individual with NDD. Inheritance was paternal (heterozygous). The variant was reviewed according to current ACMG recommendations and classified as Pathogenic (criteria: PSV1_VeryStrong, PM2_Supporting, PS3_Moderate, PM3_Moderate). This variant was identified in a compound heterozygous state with the variant NM_016038.4(SBDS):c.258+2T>C (Variation ID: 3196). (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Shwachman-Diamond syndrome 1
Affected status: yes
Allele origin:
germline
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Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine
Accession: SCV002073334.1
First in ClinVar: Feb 04, 2022 Last updated: Feb 04, 2022 |
Comment:
The stop gained p.K62* in SBDS (NM_016038.4) has been previously reported as c.183_184delinsCT. It is known to occur both in cis with 258+2T>C as a … (more)
The stop gained p.K62* in SBDS (NM_016038.4) has been previously reported as c.183_184delinsCT. It is known to occur both in cis with 258+2T>C as a complex allele due to gene conversion as well as in trans with c.258+2T>C. The variant is one amongst the three common pathogenic variants, all arising due to gene conversion with the highly homologous pseudogene SBDSP (Nelson AS et al,2018). This variant is predicted to cause loss of normal protein function through protein truncation. Functional studies demonstrate loss of function (Orelio et al,2011). The variant has been submitted to ClinVar as Pathogenic. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Cyanosis (present) , Jaundice (present)
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Pathogenic
(May 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Shwachman-Diamond syndrome 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Bioinformatics Unit, Institut Pasteur de Montevideo
Accession: SCV002505972.1
First in ClinVar: May 07, 2022 Last updated: May 07, 2022 |
Sex: female
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Pathogenic
(Sep 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Shwachman-Diamond syndrome 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175673.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The SBDS c.184A>T variant is classified as PATHOGENIC (PVS1, PS3, PS4, PM3) The SBDS c.184A>T variant is a single nucleotide change which is predicted to … (more)
The SBDS c.184A>T variant is classified as PATHOGENIC (PVS1, PS3, PS4, PM3) The SBDS c.184A>T variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 62 (PVS1). This variant has been reported many times in conjunction with a second pathogenic variant (NM_016038.4(SBDS):c.258+2T>C) in association with Shwachman-Diamond syndrome (PS4), as is the case with this patient (PM3). Functional studies have shown this variant affects the protein's cellular localisation and motility (PMID:21695142) (PS3). The variant has been reported in dbSNP (rs120074160) and in the HGMD database: CP035464. It has been reported as Pathogenic/Likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 449095). (less)
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Pathogenic
(Sep 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Shwachman-Diamond syndrome 1
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002019991.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001800138.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807443.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955842.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001973220.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome. | Orelio C | PloS one | 2011 | PMID: 21695142 |
Text-mined citations for rs120074160 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.