The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been shared with similarly affected sibling (3billion dataset) Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.2537del (p.Phe846fs)
Germline
Classification
Help
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.
(1)
Help
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.
Likely pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000548.5(TSC2):c.2537del (p.Phe846fs)
Variation ID: 1705633 Accession: VCV001705633.1
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 16p13.3 16: 2074380 (GRCh38) [ NCBI UCSC ] 16: 2124381 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 17, 2022 Sep 17, 2022 Sep 1, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.2537del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Phe846fs frameshift NM_001077183.3:c.2537del NP_001070651.1:p.Phe846fs frameshift NM_001114382.3:c.2537del NP_001107854.1:p.Phe846fs frameshift NM_001318827.2:c.2426del NP_001305756.1:p.Phe809fs frameshift NM_001318829.2:c.2390del NP_001305758.1:p.Phe797fs frameshift NM_001318831.2:c.1937del NP_001305760.1:p.Phe646fs frameshift NM_001318832.2:c.2570del NP_001305761.1:p.Phe857fs frameshift NM_001363528.2:c.2537del NP_001350457.1:p.Phe846fs frameshift NM_001370404.1:c.2537del NP_001357333.1:p.Phe846fs frameshift NM_001370405.1:c.2537del NP_001357334.1:p.Phe846fs frameshift NM_001406663.1:c.2537delT NP_001393592.1:p.Phe846Serfs frameshift NM_001406664.1:c.2537delT NP_001393593.1:p.Phe846Serfs frameshift NM_001406665.1:c.2537delT NP_001393594.1:p.Phe846Serfs frameshift NM_001406667.1:c.2627delT NP_001393596.1:p.Phe876Serfs frameshift NM_001406668.1:c.2627delT NP_001393597.1:p.Phe876Serfs frameshift NM_001406670.1:c.2426delT NP_001393599.1:p.Phe809Serfs frameshift NM_001406671.1:c.2525delT NP_001393600.1:p.Phe842Serfs frameshift NM_001406673.1:c.2525delT NP_001393602.1:p.Phe842Serfs frameshift NM_001406675.1:c.2390delT NP_001393604.1:p.Phe797Serfs frameshift NM_001406676.1:c.2390delT NP_001393605.1:p.Phe797Serfs frameshift NM_001406677.1:c.2480delT NP_001393606.1:p.Phe827Serfs frameshift NM_001406678.1:c.2426delT NP_001393607.1:p.Phe809Serfs frameshift NM_001406679.1:c.2390delT NP_001393608.1:p.Phe797Serfs frameshift NM_001406680.1:c.1937delT NP_001393609.1:p.Phe646Serfs frameshift NM_001406681.1:c.2075delT NP_001393610.1:p.Phe692Serfs frameshift NM_001406682.1:c.1937delT NP_001393611.1:p.Phe646Serfs frameshift NM_001406683.1:c.1937delT NP_001393612.1:p.Phe646Serfs frameshift NM_001406684.1:c.1937delT NP_001393613.1:p.Phe646Serfs frameshift NM_001406685.1:c.1937delT NP_001393614.1:p.Phe646Serfs frameshift NM_001406686.1:c.1937delT NP_001393615.1:p.Phe646Serfs frameshift NM_001406687.1:c.1937delT NP_001393616.1:p.Phe646Serfs frameshift NM_001406688.1:c.1937delT NP_001393617.1:p.Phe646Serfs frameshift NM_001406689.1:c.1193delT NP_001393618.1:p.Phe398Serfs frameshift NM_001406690.1:c.1193delT NP_001393619.1:p.Phe398Serfs frameshift NM_001406691.1:c.1193delT NP_001393620.1:p.Phe398Serfs frameshift NM_001406692.1:c.1193delT NP_001393621.1:p.Phe398Serfs frameshift NM_001406693.1:c.1193delT NP_001393622.1:p.Phe398Serfs frameshift NM_001406694.1:c.1193delT NP_001393623.1:p.Phe398Serfs frameshift NM_001406695.1:c.1193delT NP_001393624.1:p.Phe398Serfs frameshift NM_001406696.1:c.1193delT NP_001393625.1:p.Phe398Serfs frameshift NM_001406697.1:c.1193delT NP_001393626.1:p.Phe398Serfs frameshift NM_001406698.1:c.935delT NP_001393627.1:p.Phe312Serfs frameshift NM_021055.3:c.2537del NP_066399.2:p.Phe846fs frameshift NR_176225.1:n.2687delT NR_176226.1:n.2866delT NR_176227.1:n.2866delT NR_176228.1:n.2687delT NR_176229.1:n.2647delT NC_000016.10:g.2074381del NC_000016.9:g.2124382del NG_005895.1:g.30076del LRG_487:g.30076del LRG_487t1:c.2537del LRG_487p1:p.Phe846Serfs - Protein change
- F646fs, F797fs, F809fs, F846fs, F857fs
- Other names
- -
- Canonical SPDI
- NC_000016.10:2074379:TT:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10758 | 10957 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
|
Sep 1, 2022 | RCV002283947.1 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Sep 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002573201.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been shared with similarly affected sibling (3billion dataset) Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Seizure (present) , Global developmental delay (present) , Hypopigmented skin patches (present)
|
Comment:
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. |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been shared with similarly affected sibling (3billion dataset) Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Nov 05, 2022
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.