VCV002500143.2 - ClinVar

NM_016188.5(ACTL6B):c.703AAG[2] (p.Lys237del)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Uncertain significance

1 out of 2 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_016188.5(ACTL6B):c.703AAG[2] (p.Lys237del)

Variation ID: 2500143 Accession: VCV002500143.2

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: 7q22.1 7: 100647492-100647494 (GRCh38) [ NCBI UCSC ] 7: 100245115-100245117 (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	Oct 7, 2023	Jun 14, 2025	Dec 9, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_016188.5:c.703AAG[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057272.1:p.Lys237del	inframe deletion
NR_134539.2:n.797AAG[2]		non-coding transcript variant
NC_000007.14:g.100647493TTC[2]
NC_000007.13:g.100245116TTC[2]

Protein change

K237del

Other names

Canonical SPDI

NC_000007.14:100647491:CTTCTTCTTC:CTTCTTC

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

ClinGen: CA1105051954 dbSNP: rs755552228 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.
ACTL6B		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	159	185

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.
Developmental and epileptic encephalopathy, 76	Pathogenic (1)	no assertion criteria provided	-	RCV003331539.2
not provided	Uncertain significance (1)	criteria provided, single submitter	Dec 9, 2024	RCV005416710.1

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.	Expand all rows Collapse all rows 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 (Dec 09, 2024) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Not Provided	GeneDx Accession: SCV006083900.1 First in ClinVar: Jun 14, 2025 Last updated: Jun 14, 2025	Comment: show Observed in an individual with a neurodevelopmental disorder in published literature, but additional clinical information was not provided (PMID: 37500730); Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid(s) in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 37500730) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (-) N Not contributing to aggregate classification	no assertion criteria provided	Developmental and epileptic encephalopathy, 76	Houlden Lab, UCL Institute of Neurology Accession: SCV003920667.1 First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 Comment: This variant was identified in a compound heterozygous state with another ACTL6B variant (c.695_696insC) for this condition.	Observation: 1 Collection method: research Allele origin: germline Affected status: yes more Observation 1 Collection method: research Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Comment:

Observed in an individual with a neurodevelopmental disorder in published literature, but additional clinical information was not provided (PMID: 37500730); Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid(s) in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 37500730)

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 rs755552228 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2025