ClinVar Genomic variation as it relates to human health
NM_022455.5(NSD1):c.2049_2053del (p.Ile684fs)
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_022455.5(NSD1):c.2049_2053del (p.Ile684fs)
Variation ID: 159277 Accession: VCV000159277.15
- Type and length
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Deletion, 5 bp
- Location
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Cytogenetic: 5q35.3 5: 177210446-177210450 (GRCh38) [ NCBI UCSC ] 5: 176637447-176637451 (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 Nov 23, 2014 Feb 7, 2023 Aug 26, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_022455.5:c.2049_2053del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_071900.2:p.Ile684fs frameshift NM_001365684.2:c.1176_1180delGATAA NP_001352613.2:p.Ile393Valfs frameshift NM_001409301.1:c.2049_2053delGATAA NP_001396230.1:p.Ile684Valfs frameshift NM_001409302.1:c.2049_2053delGATAA NP_001396231.1:p.Ile684Valfs frameshift NM_001409303.1:c.2049_2053delGATAA NP_001396232.1:p.Ile684Valfs frameshift NM_001409304.1:c.1629_1633delGATAA NP_001396233.1:p.Ile544Valfs frameshift NM_001409305.1:c.1296_1300delGATAA NP_001396234.1:p.Ile433Valfs frameshift NM_001409306.1:c.1176_1180delGATAA NP_001396235.1:p.Ile393Valfs frameshift NM_001409307.1:c.1176_1180delGATAA NP_001396236.1:p.Ile393Valfs frameshift NM_001409308.1:c.1176_1180delGATAA NP_001396237.1:p.Ile393Valfs frameshift NM_001409309.1:c.1176_1180delGATAA NP_001396238.1:p.Ile393Valfs frameshift NM_022455.4:c.2049_2053delGATAA NP_071900.2:p.Ile684Valfs frameshift NM_172349.5:c.1176_1180delGATAA NP_758859.2:p.Ile393Valfs frameshift NC_000005.10:g.177210448_177210452del NC_000005.9:g.176637449_176637453del NG_009821.1:g.82370_82374del LRG_512:g.82370_82374del LRG_512t1:c.2049_2053del LRG_512p1:p.Ile684fs - Protein change
- I415fs, I684fs
- Other names
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- Canonical SPDI
- NC_000005.10:177210445:AAGATAA:AA
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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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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NSD1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1656 | 1768 |
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
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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 (3) |
criteria provided, multiple submitters, no conflicts
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Aug 26, 2021 | RCV003231181.8 |
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
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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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Pathogenic
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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Sotos syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000194101.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Sotos syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002054915.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
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Pathogenic
(Aug 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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None
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001203752.4
First in ClinVar: Apr 15, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Ile684Valfs*3) in the NSD1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ile684Valfs*3) in the NSD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with overgrowth syndrome (PMID: 28475857). ClinVar contains an entry for this variant (Variation ID: 159277). For these reasons, this variant has been classified as Pathogenic. (less)
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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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Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability. | Tatton-Brown K | American journal of human genetics | 2017 | PMID: 28475857 |
NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory. | Waggoner DJ | Genetics in medicine : official journal of the American College of Medical Genetics | 2005 | PMID: 16247291 |
Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. | Tatton-Brown K | American journal of human genetics | 2005 | PMID: 15942875 |
Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes. | Türkmen S | European journal of human genetics : EJHG | 2003 | PMID: 14571271 |
NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. | Douglas J | American journal of human genetics | 2003 | PMID: 12464997 |
Text-mined citations for rs587784080 ...
HelpRecord last updated Apr 20, 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.