VCV001801704.4 - ClinVar

NM_182931.3(KMT2E):c.2881_2882del (p.Lys961fs)

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.

(4)

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/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_182931.3(KMT2E):c.2881_2882del (p.Lys961fs)

Variation ID: 1801704 Accession: VCV001801704.4

Type and length

Deletion, 2 bp

Location

Cytogenetic: 7q22.3 7: 105107198-105107199 (GRCh38) [ NCBI UCSC ] 7: 104747645-104747646 (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	Dec 11, 2022	Nov 24, 2024	Nov 12, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_182931.3:c.2881_2882del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_891847.1:p.Lys961fs	frameshift
NM_001410908.1:c.2881_2882delAA	NP_001397837.1:p.Lys961Glufs	frameshift
NM_018682.4:c.2880_2881del
NM_018682.4:c.2881_2882del	NP_061152.3:p.Lys961fs	frameshift
NC_000007.14:g.105107199_105107200del
NC_000007.13:g.104747646_104747647del
NG_033949.1:g.98010_98011del
LRG_1404:g.98010_98011del
LRG_1404t1:c.2881_2882del	LRG_1404p1:p.Lys961fs

... more HGVS ... less HGVS

Protein change

K961fs

Other names

Canonical SPDI

NC_000007.14:105107197:AAA:A

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.
KMT2E		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	951	983

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.
Global developmental delay	Likely pathogenic (1)	criteria provided, single submitter	Mar 1, 2022	RCV002463863.4
O'Donnell-Luria-Rodan syndrome	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Nov 12, 2024	RCV003329125.4
not provided	Likely pathogenic (1)	no assertion criteria provided	Sep 6, 2021	RCV003325318.3

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 (Mar 01, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Global developmental delay Affected status: yes Allele origin: germline	Human Genetics Bochum, Ruhr University Bochum Accession: SCV002758634.1 First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022	Comment: ACMG criteria used to clasify this variant: PVS1, PM2_SUP
Likely pathogenic (Aug 09, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: provider interpretation	O'Donnell-Luria-Rodan syndrome (Autosomal dominant inheritance) Affected status: yes Allele origin: de novo	Pediatrics, Sichuan Provincial Hospital For Women And Children Accession: SCV004031466.1 First in ClinVar: Sep 23, 2023 Last updated: Sep 23, 2023	Comment: Drug refractory epilepsy，epileptic spasms，Global development delay Clinical Features: Epileptic spasm (present) , Global developmental delay (present) Age: 0-9 years Sex: female Testing laboratory: Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Hospital for Women and Children,
Pathogenic (Nov 12, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	O'Donnell-Luria-Rodan syndrome Affected status: yes Allele origin: de novo	Translational Cytogenomics Research Unit, Bambino Gesu Children Hospital Accession: SCV005397955.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Comment: Null variant (frame-shift) in gene KMT2E, predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 104 reported pathogenic LOF variants). The … (more) Null variant (frame-shift) in gene KMT2E, predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 104 reported pathogenic LOF variants). The exon affects 1 functional domain: UniProt protein KMT2E_HUMAN region of interest 'Disordered'. The truncated region contains 46 pathogenic variants. ClinVar classifies this variant as Likely Pathogenic, 2 stars (reviewed Jun '24, 3 submissions - Variation ID: 1801704), associated with O'Donnell-Luria-Rodan Syndrome. This variant has been identified as a de novo. ACMG Criteria (PVS1, PP5, PM2, PS2) (less) Sex: female
Likely pathogenic (Sep 06, 2021)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: de novo	Molecular Genetics laboratory, Necker Hospital Accession: SCV004031271.1 First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023	Clinical Features: Intellectual disability (present)

Comment:

Null variant (frame-shift) in gene KMT2E, predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 104 reported pathogenic LOF variants). The exon affects 1 functional domain: UniProt protein KMT2E_HUMAN region of interest 'Disordered'. The truncated region contains 46 pathogenic variants. ClinVar classifies this variant as Likely Pathogenic, 2 stars (reviewed Jun '24, 3 submissions - Variation ID: 1801704), associated with O'Donnell-Luria-Rodan Syndrome. This variant has been identified as a de novo. ACMG Criteria (PVS1, PP5, PM2, PS2)

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 Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_182931.3(KMT2E):c.2881_2882del (p.Lys961fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...