The observed missense c.994A>T (p.Met332Leu) variant in CELF2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Met332Leu variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Met332Leu in CELF2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Met at position 332 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).
ClinVar Genomic variation as it relates to human health
NM_001326342.2(CELF2):c.1015A>T (p.Met339Leu)
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001326342.2(CELF2):c.1015A>T (p.Met339Leu)
Variation ID: 3377600 Accession: VCV003377600.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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10: 11314177 (GRCh38) [ NCBI UCSC ] 10: 11356140 (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 25, 2024 Nov 24, 2024 Jun 22, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001326342.2:c.1015A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001313271.1:p.Met339Leu missense NM_001025076.2:c.922A>T NP_001020247.1:p.Met308Leu missense NM_001025077.3:c.994A>T NP_001020248.1:p.Met332Leu missense NM_001083591.1:c.922A>T NP_001077060.1:p.Met308Leu missense NM_001326317.2:c.922A>T NP_001313246.1:p.Met308Leu missense NM_001326318.2:c.922A>T NP_001313247.1:p.Met308Leu missense NM_001326319.2:c.922A>T NP_001313248.1:p.Met308Leu missense NM_001326320.2:c.922A>T NP_001313249.1:p.Met308Leu missense NM_001326321.2:c.922A>T NP_001313250.1:p.Met308Leu missense NM_001326323.2:c.922A>T NP_001313252.1:p.Met308Leu missense NM_001326324.2:c.922A>T NP_001313253.1:p.Met308Leu missense NM_001326325.2:c.1087A>T NP_001313254.1:p.Met363Leu missense NM_001326326.2:c.1030A>T NP_001313255.1:p.Met344Leu missense NM_001326327.2:c.1030A>T NP_001313256.1:p.Met344Leu missense NM_001326328.2:c.922A>T NP_001313257.1:p.Met308Leu missense NM_001326329.2:c.922A>T NP_001313258.1:p.Met308Leu missense NM_001326330.2:c.922A>T NP_001313259.1:p.Met308Leu missense NM_001326331.2:c.994A>T NP_001313260.1:p.Met332Leu missense NM_001326332.2:c.994A>T NP_001313261.1:p.Met332Leu missense NM_001326333.2:c.310A>T NP_001313262.1:p.Met104Leu missense NM_001326334.2:c.922A>T NP_001313263.1:p.Met308Leu missense NM_001326335.2:c.994A>T NP_001313264.1:p.Met332Leu missense NM_001326336.2:c.994A>T NP_001313265.1:p.Met332Leu missense NM_001326337.2:c.994A>T NP_001313266.1:p.Met332Leu missense NM_001326338.2:c.661A>T NP_001313267.1:p.Met221Leu missense NM_001326339.2:c.661A>T NP_001313268.1:p.Met221Leu missense NM_001326340.2:c.1015A>T NP_001313269.1:p.Met339Leu missense NM_001326341.2:c.1015A>T NP_001313270.1:p.Met339Leu missense NM_001326343.2:c.1015A>T NP_001313272.1:p.Met339Leu missense NM_001326344.2:c.922A>T NP_001313273.1:p.Met308Leu missense NM_001326345.2:c.922A>T NP_001313274.1:p.Met308Leu missense NM_001326346.2:c.310A>T NP_001313275.1:p.Met104Leu missense NM_001326347.1:c.946A>T NP_001313276.1:p.Met316Leu missense NM_001326348.2:c.922A>T NP_001313277.1:p.Met308Leu missense NM_001326349.2:c.922A>T NP_001313278.1:p.Met308Leu missense NM_001394502.1:c.994A>T NP_001381431.1:p.Met332Leu missense NM_001394513.1:c.1015A>T NP_001381442.1:p.Met339Leu missense NM_001394517.1:c.922A>T NP_001381446.1:p.Met308Leu missense NM_001394518.1:c.1015A>T NP_001381447.1:p.Met339Leu missense NM_001394519.1:c.1015A>T NP_001381448.1:p.Met339Leu missense NM_006561.4:c.1015A>T NP_006552.3:p.Met339Leu missense NC_000010.11:g.11314177A>T NC_000010.10:g.11356140A>T - Protein change
- M104L, M221L, M308L, M316L, M332L, M339L, M344L, M363L
- Other names
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- Canonical SPDI
- NC_000010.11:11314176:A:T
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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
Help
The frequency of the allele represented by this VCV record.
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- 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. |
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| CELF2 | - | - |
GRCh38 GRCh37 |
39 | 89 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Jun 22, 2023 | RCV004785775.1 |
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. |
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Uncertain significance
(Jun 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Developmental and epileptic encephalopathy, 14
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005400794.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
The observed missense c.994A>T (p.Met332Leu) variant in CELF2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our … (more)
The observed missense c.994A>T (p.Met332Leu) variant in CELF2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Met332Leu variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Met332Leu in CELF2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Met at position 332 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). (less)
Clinical Features:
Abnormality of the nervous system (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 observed missense c.994A>T (p.Met332Leu) variant in CELF2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Met332Leu variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid of p.Met332Leu in CELF2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Met at position 332 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).
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 25, 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.