VCV002735647.1 - ClinVar

NM_001370259.2(MEN1):c.1351-4_1352del

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.

Uncertain significance

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.1351-4_1352del

Variation ID: 2735647 Accession: VCV002735647.1

Type and length

Deletion, 6 bp

Location

Cytogenetic: 11q13.1 11: 64804815-64804820 (GRCh38) [ NCBI UCSC ] 11: 64572287-64572292 (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	Feb 14, 2024	Feb 14, 2024	Aug 31, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370259.2:c.1351-4_1352del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor
NM_000244.4:c.1366-4_1367del		splice acceptor
NM_001370251.2:c.1477-4_1478del		splice acceptor
NM_001370260.2:c.1351-4_1352del		splice acceptor
NM_001370261.2:c.1351-4_1352del		splice acceptor
NM_001370262.2:c.1246-4_1247del		splice acceptor
NM_001370263.2:c.1246-4_1247del		splice acceptor
NM_001407142.1:c.1477-4_1478del		splice acceptor
NM_001407143.1:c.1477-4_1478del		splice acceptor
NM_001407144.1:c.1477-4_1478del		splice acceptor
NM_001407145.1:c.1366-4_1367del		splice acceptor
NM_001407146.1:c.1351-4_1352del		splice acceptor
NM_001407147.1:c.1351-4_1352del		splice acceptor
NM_001407148.1:c.1246-4_1247del		splice acceptor
NM_001407149.1:c.1246-4_1247del		splice acceptor
NM_001407150.1:c.1492-4_1493del		splice acceptor
NM_001407151.1:c.1372-4_1373del		splice acceptor
NM_001407152.1:c.1186-4_1187del		splice acceptor
NM_130799.3:c.1351-4_1352del		splice acceptor
NM_130800.3:c.1366-4_1367del		splice acceptor
NM_130801.3:c.1366-4_1367del		splice acceptor
NM_130802.3:c.1366-4_1367del		splice acceptor
NM_130803.3:c.1366-4_1367del		splice acceptor
NM_130804.3:c.1366-4_1367del		splice acceptor
NC_000011.10:g.64804815_64804820del
NC_000011.9:g.64572287_64572292del
NG_008929.1:g.11475_11480del
NG_033040.1:g.3422_3427del
NG_033040.2:g.3394_3399del
LRG_509:g.11475_11480del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:64804814:ACCTGG:

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.
Multiple endocrine neoplasia, type 1	Uncertain significance (1)	criteria provided, single submitter	Aug 31, 2023	RCV003518776.2

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.
Uncertain significance (Aug 31, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Multiple endocrine neoplasia, type 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004295810.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 16563611‚ 17576681‚ 9536098 Comment: In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more) In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant results in the deletion of part of exon 10 (c.1351-4_1352del) of the MEN1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hyperparathyroidism (PMID: 16563611). This variant is also known as IVS9-4del6. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). (less)

Comment:

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant results in the deletion of part of exon 10 (c.1351-4_1352del) of the MEN1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hyperparathyroidism (PMID: 16563611). This variant is also known as IVS9-4del6. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098).

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

Title	Author	Journal	Year	Link
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.	Buratti E	Nucleic acids research	2007	PMID: 17576681
Characteristics of the Danish families with multiple endocrine neoplasia type 1.	Jäger AC	Molecular and cellular endocrinology	2006	PMID: 16563611
Statistical features of human exons and their flanking regions.	Zhang MQ	Human molecular genetics	1998	PMID: 9536098

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_001370259.2(MEN1):c.1351-4_1352del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...