VCV003062048.1 - ClinVar

NM_177438.3(DICER1):c.4909_4910del (p.Ser1637fs)

Germline

Classification

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)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_177438.3(DICER1):c.4909_4910del (p.Ser1637fs)

Variation ID: 3062048 Accession: VCV003062048.1

Type and length

Deletion, 2 bp

Location

Cytogenetic: 14q32.13 14: 95096010-95096011 (GRCh38) [ NCBI UCSC ] 14: 95562347-95562348 (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	Mar 23, 2024	Mar 23, 2024	Apr 30, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_177438.3:c.4909_4910del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_803187.1:p.Ser1637fs	frameshift
NM_001195573.1:c.4909_4910del	NP_001182502.1:p.Ser1637fs	frameshift
NM_001271282.3:c.4909_4910del	NP_001258211.1:p.Ser1637fs	frameshift
NM_001291628.2:c.4909_4910del	NP_001278557.1:p.Ser1637fs	frameshift
NM_001395677.1:c.4909_4910del	NP_001382606.1:p.Ser1637fs	frameshift
NM_001395678.1:c.4909_4910del	NP_001382607.1:p.Ser1637fs	frameshift
NM_001395679.1:c.4909_4910del	NP_001382608.1:p.Ser1637fs	frameshift
NM_001395680.1:c.4909_4910del	NP_001382609.1:p.Ser1637fs	frameshift
NM_001395681.1:c.4908_4909delCT	NP_001382610.1:p.Ser1637Glyfs	frameshift
NM_001395682.1:c.4909_4910del	NP_001382611.1:p.Ser1637fs	frameshift
NM_001395683.1:c.4909_4910del	NP_001382612.1:p.Ser1637fs	frameshift
NM_001395684.1:c.4909_4910del	NP_001382613.1:p.Ser1637fs	frameshift
NM_001395686.1:c.4627_4628del	NP_001382615.1:p.Ser1543fs	frameshift
NM_001395687.1:c.4504_4505del	NP_001382616.1:p.Ser1502fs	frameshift
NM_001395688.1:c.4504_4505del	NP_001382617.1:p.Ser1502fs	frameshift
NM_001395689.1:c.4504_4505del	NP_001382618.1:p.Ser1502fs	frameshift
NM_001395690.1:c.4504_4505del	NP_001382619.1:p.Ser1502fs	frameshift
NM_001395691.1:c.4342_4343del	NP_001382620.1:p.Ser1448fs	frameshift
NM_001395692.1:c.4909_4910del	NP_001382621.1:p.Ser1637fs	frameshift
NM_001395693.1:c.4909_4910del	NP_001382622.1:p.Ser1637fs	frameshift
NM_001395694.1:c.4909_4910del	NP_001382623.1:p.Ser1637fs	frameshift
NM_001395695.1:c.4909_4910del	NP_001382624.1:p.Ser1637fs	frameshift
NM_001395696.1:c.4504_4505del	NP_001382625.1:p.Ser1502fs	frameshift
NM_001395697.1:c.3226_3227del	NP_001382626.1:p.Ser1076fs	frameshift
NM_030621.4:c.4909_4910del	NP_085124.2:p.Ser1637fs	frameshift
NR_172715.1:n.5327_5328del		non-coding transcript variant
NR_172716.1:n.5511_5512del		non-coding transcript variant
NR_172717.1:n.5421_5422del		non-coding transcript variant
NR_172718.1:n.5344_5345del		non-coding transcript variant
NR_172719.1:n.5177_5178del		non-coding transcript variant
NR_172720.1:n.5254_5255del		non-coding transcript variant
NC_000014.9:g.95096011_95096012del
NC_000014.8:g.95562348_95562349del
NG_016311.1:g.66412_66413del
LRG_492:g.66412_66413del
LRG_492t1:c.4908_4909del	LRG_492p1:p.Ser1637Glyfs

... more HGVS ... less HGVS

Protein change

S1076fs, S1448fs, S1502fs, S1543fs, S1637fs

Other names

Canonical SPDI

NC_000014.9:95096009:GAG:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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

VarSome

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
Gene	OMIM	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.
DICER1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	6484	6522

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.
DICER1-related tumor predisposition	Likely pathogenic (1)	criteria provided, single submitter	Apr 30, 2019	RCV003985158.1

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 (Apr 30, 2019)	criteria provided, single submitter (ICSLVariantClassificationCriteria RUGD 01 April 2020) Method: clinical testing	DICER1-related tumor predisposition Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV004801460.1 First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024	Comment: The DICER1 c.4909_4910delTC p.(Ser1637GlyfsTer14) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss … (more) The DICER1 c.4909_4910delTC p.(Ser1637GlyfsTer14) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Based on the available evidence the c.4909_4910delTC p.(Ser1637GlyfsTer14) variant is classified as likely pathogenic for DICER1-related tumor susceptibility syndrome. (less)

Comment:

The DICER1 c.4909_4910delTC p.(Ser1637GlyfsTer14) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Based on the available evidence the c.4909_4910delTC p.(Ser1637GlyfsTer14) variant is classified as likely pathogenic for DICER1-related tumor susceptibility syndrome.

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:

Citations for germline classification of this variant

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 ...

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_177438.3(DICER1):c.4909_4910del (p.Ser1637fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...