VCV001709560.2 - ClinVar

NM_001130438.3(SPTAN1):c.6896_6904del (p.Trp2299_Gln2301del)

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.

(2)

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.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130438.3(SPTAN1):c.6896_6904del (p.Trp2299_Gln2301del)

Variation ID: 1709560 Accession: VCV001709560.2

Type and length

Deletion, 9 bp

Location

Cytogenetic: 9q34.11 9: 128632260-128632268 (GRCh38) [ NCBI UCSC ] 9: 131394539-131394547 (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 15, 2022	May 1, 2024	Feb 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130438.3:c.6896_6904del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001123910.1:p.Trp2299_Gln2301del	inframe deletion
NM_001130438.2:c.6896_6904delGGGACCAGC
NM_001195532.2:c.6821_6829del	NP_001182461.1:p.Trp2274_Gln2276del	inframe deletion
NM_001363759.2:c.6959_6967del	NP_001350688.1:p.Trp2320_Gln2322del	inframe deletion
NM_001363765.2:c.6836_6844del	NP_001350694.1:p.Trp2279_Gln2281del	inframe deletion
NM_001375310.1:c.6983_6991del	NP_001362239.1:p.Trp2328_Gln2330del	inframe deletion
NM_001375311.2:c.6896_6904del	NP_001362240.1:p.Trp2299_Gln2301del	inframe deletion
NM_001375312.2:c.6932_6940del	NP_001362241.2:p.Trp2311_Gln2313del	inframe deletion
NM_001375313.1:c.6878_6886del	NP_001362242.1:p.Trp2293_Gln2295del	inframe deletion
NM_001375314.2:c.6836_6844del	NP_001362243.1:p.Trp2279_Gln2281del	inframe deletion
NM_001375318.1:c.6995_7003del	NP_001362247.1:p.Trp2332_Gln2334del	inframe deletion
NM_003127.4:c.6881_6889del	NP_003118.2:p.Trp2294_Gln2296del	inframe deletion
NC_000009.12:g.128632260_128632268del
NC_000009.11:g.131394539_131394547del
NG_027748.2:g.84675_84683del
NG_034056.1:g.29583_29591del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000009.12:128632259:GGGACCAGC:

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.
SPTAN1		-	-	GRCh38 GRCh37	2640	2699

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, 5	Pathogenic (1)	criteria provided, single submitter	Aug 27, 2021	RCV002289375.2
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Feb 29, 2024	RCV004047607.1

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.
Pathogenic (Aug 27, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Developmental and epileptic encephalopathy, 5 Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002580196.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PS2_VSTR, PM1, PM4, PM2_SUP	Number of individuals with the variant: 1 Sex: male
Uncertain significance (Feb 29, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV004956298.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.6896_6904delGGGACCAGC (p.W2299_Q2301del) alteration, located in coding exon 52 of the SPTAN1 gene, results from an in-frame deletion of 9 nucleotides at positions c.6896 to … (more) The c.6896_6904delGGGACCAGC (p.W2299_Q2301del) alteration, located in coding exon 52 of the SPTAN1 gene, results from an in-frame deletion of 9 nucleotides at positions c.6896 to c.6904. This results in the deletion of 3 amino acids between codons 2299 and 2301. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). These amino acid positions are highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)

Comment:

The c.6896_6904delGGGACCAGC (p.W2299_Q2301del) alteration, located in coding exon 52 of the SPTAN1 gene, results from an in-frame deletion of 9 nucleotides at positions c.6896 to c.6904. This results in the deletion of 3 amino acids between codons 2299 and 2301. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). These amino acid positions are highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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 08, 2024

ClinVar Genomic variation as it relates to human health

NM_001130438.3(SPTAN1):c.6896_6904del (p.Trp2299_Gln2301del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...