VCV001771268.2 - ClinVar

NM_001370259.2(MEN1):c.1380_1383del (p.Glu461fs)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001370259.2(MEN1):c.1380_1383del (p.Glu461fs)

Variation ID: 1771268 Accession: VCV001771268.2

Type and length

Deletion, 4 bp

Location

Cytogenetic: 11q13.1 11: 64804784-64804787 (GRCh38) [ NCBI UCSC ] 11: 64572256-64572259 (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	Nov 29, 2022	May 1, 2024	Oct 12, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370259.2:c.1380_1383del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357188.2:p.Glu461fs	frameshift
NM_000244.4:c.1395_1398del	NP_000235.3:p.Glu466fs	frameshift
NM_001370251.2:c.1506_1509del	NP_001357180.2:p.Glu503fs	frameshift
NM_001370260.2:c.1380_1383del	NP_001357189.2:p.Glu461fs	frameshift
NM_001370261.2:c.1380_1383del	NP_001357190.2:p.Glu461fs	frameshift
NM_001370262.2:c.1275_1278del	NP_001357191.2:p.Glu426fs	frameshift
NM_001370263.2:c.1275_1278del	NP_001357192.2:p.Glu426fs	frameshift
NM_001407142.1:c.1505_1508delGAGA	NP_001394071.1:p.Glu503Profs	frameshift
NM_001407143.1:c.1505_1508delGAGA	NP_001394072.1:p.Glu503Profs	frameshift
NM_001407144.1:c.1505_1508delGAGA	NP_001394073.1:p.Glu503Profs	frameshift
NM_001407145.1:c.1394_1397delGAGA	NP_001394074.1:p.Glu466Profs	frameshift
NM_001407146.1:c.1379_1382delGAGA	NP_001394075.1:p.Glu461Profs	frameshift
NM_001407147.1:c.1379_1382delGAGA	NP_001394076.1:p.Glu461Profs	frameshift
NM_001407148.1:c.1274_1277delGAGA	NP_001394077.1:p.Glu426Profs	frameshift
NM_001407149.1:c.1274_1277delGAGA	NP_001394078.1:p.Glu426Profs	frameshift
NM_001407150.1:c.1520_1523delGAGA	NP_001394079.1:p.Glu508Profs	frameshift
NM_001407151.1:c.1400_1403delGAGA	NP_001394080.1:p.Glu468Profs	frameshift
NM_001407152.1:c.1214_1217delGAGA	NP_001394081.1:p.Glu406Profs	frameshift
NM_130799.2:c.1380_1383delAGAG		frameshift
NM_130799.3:c.1380_1383del	NP_570711.2:p.Glu461fs	frameshift
NM_130800.3:c.1395_1398del	NP_570712.2:p.Glu466fs	frameshift
NM_130801.3:c.1395_1398del	NP_570713.2:p.Glu466fs	frameshift
NM_130802.3:c.1395_1398del	NP_570714.2:p.Glu466fs	frameshift
NM_130803.3:c.1395_1398del	NP_570715.2:p.Glu466fs	frameshift
NM_130804.3:c.1395_1398del	NP_570716.2:p.Glu466fs	frameshift
NR_176284.1:n.1577_1580delGAGA
NR_176285.1:n.1589_1592delGAGA
NR_176286.1:n.1592_1595delGAGA
NR_176287.1:n.1850_1853delGAGA
NC_000011.10:g.64804785_64804788del
NC_000011.9:g.64572257_64572260del
NG_008929.1:g.11508_11511del
NG_033040.2:g.3427_3430del
LRG_509:g.11508_11511del
LRG_509t1:c.1394_1397del	LRG_509p1:p.Glu466Profs
LRG_509t2:c.1379_1382del	LRG_509p2:p.Glu461Profs

... more HGVS ... less HGVS

Protein change

E503fs, E461fs, E466fs, E426fs

Other names

Canonical SPDI

NC_000011.10:64804783:CTCTC:C

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.
MEN1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2580	2601

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.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Oct 12, 2022	RCV002381146.2

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.
Pathogenic (Oct 12, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002696729.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: The c.1380_1383delAGAG pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a deletion of 4 nucleotides at nucleotide positions 1380 to … (more) The c.1380_1383delAGAG pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a deletion of 4 nucleotides at nucleotide positions 1380 to 1383, causing a translational frameshift with a predicted alternate stop codon (p.E461Pfs*97). This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 150 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This alteration has been observed in at least one individual with features consistent with MEN1-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)

Comment:

The c.1380_1383delAGAG pathogenic mutation, located in coding exon 9 of the MEN1 gene, results from a deletion of 4 nucleotides at nucleotide positions 1380 to 1383, causing a translational frameshift with a predicted alternate stop codon (p.E461Pfs*97). This alteration occurs at the 3' terminus of theMEN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 150 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This alteration has been observed in at least one individual with features consistent with MEN1-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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 May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_001370259.2(MEN1):c.1380_1383del (p.Glu461fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...