VCV002413847.4 - ClinVar

NM_001351169.2(NT5C2):c.1153_1154del (p.Lys385fs)

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_001351169.2(NT5C2):c.1153_1154del (p.Lys385fs)

Variation ID: 2413847 Accession: VCV002413847.4

Type and length

Deletion, 2 bp

Location

Cytogenetic: 10q24.32 10: 103093144-103093145 (GRCh38) [ NCBI UCSC ] 10: 104852901-104852902 (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 13, 2023	Feb 20, 2024	May 12, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001351169.2:c.1153_1154del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001338098.1:p.Lys385fs	frameshift
NM_001134373.3:c.1153_1154del	NP_001127845.1:p.Lys385fs	frameshift
NM_001351170.2:c.1177_1178del	NP_001338099.1:p.Lys393fs	frameshift
NM_001351171.2:c.1177_1178del	NP_001338100.1:p.Lys393fs	frameshift
NM_001351172.2:c.1177_1178del	NP_001338101.1:p.Lys393fs	frameshift
NM_001351173.2:c.1177_1178del	NP_001338102.1:p.Lys393fs	frameshift
NM_001351174.1:c.1066_1067del	NP_001338103.1:p.Lys356fs	frameshift
NM_001351175.2:c.1060_1061del	NP_001338104.1:p.Lys354fs	frameshift
NM_001351176.2:c.580_581del	NP_001338105.1:p.Lys194fs	frameshift
NM_001351177.2:c.580_581del	NP_001338106.1:p.Lys194fs	frameshift
NM_001351178.2:c.580_581del	NP_001338107.1:p.Lys194fs	frameshift
NM_001351179.2:c.580_581del	NP_001338108.1:p.Lys194fs	frameshift
NM_001351180.2:c.580_581del	NP_001338109.1:p.Lys194fs	frameshift
NM_001351181.2:c.580_581del	NP_001338110.1:p.Lys194fs	frameshift
NM_001351182.2:c.580_581del	NP_001338111.1:p.Lys194fs	frameshift
NM_001351183.2:c.580_581del	NP_001338112.1:p.Lys194fs	frameshift
NM_001351184.2:c.580_581del	NP_001338113.1:p.Lys194fs	frameshift
NM_001351185.2:c.580_581del	NP_001338114.1:p.Lys194fs	frameshift
NM_001351186.2:c.580_581del	NP_001338115.1:p.Lys194fs	frameshift
NM_001351187.2:c.580_581del	NP_001338116.1:p.Lys194fs	frameshift
NM_001351188.2:c.580_581del	NP_001338117.1:p.Lys194fs	frameshift
NM_001351189.2:c.580_581del	NP_001338118.1:p.Lys194fs	frameshift
NM_001351190.2:c.580_581del	NP_001338119.1:p.Lys194fs	frameshift
NM_001351191.1:c.580_581del	NP_001338120.1:p.Lys194fs	frameshift
NM_001351192.1:c.580_581del	NP_001338121.1:p.Lys194fs	frameshift
NM_001351193.1:c.580_581del	NP_001338122.1:p.Lys194fs	frameshift
NM_001351194.2:c.439_440del	NP_001338123.1:p.Lys147fs	frameshift
NM_001351195.2:c.439_440del	NP_001338124.1:p.Lys147fs	frameshift
NM_001351196.2:c.439_440del	NP_001338125.1:p.Lys147fs	frameshift
NM_001351197.2:c.580_581del	NP_001338126.1:p.Lys194fs	frameshift
NM_012229.5:c.1153_1154del	NP_036361.1:p.Lys385fs	frameshift
NC_000010.11:g.103093144_103093145del
NC_000010.10:g.104852901_104852902del
NG_042272.1:g.105162_105163del

... more HGVS ... less HGVS

Protein change

K147fs, K194fs, K354fs, K356fs, K385fs, K393fs

Other names

Canonical SPDI

NC_000010.11:103093143:TT:

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.
NT5C2		-	-	GRCh38 GRCh37	204	267

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 spastic paraplegia 45	Pathogenic (1)	criteria provided, single submitter	May 12, 2022	RCV003104643.5

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 (May 12, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary spastic paraplegia 45 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003781487.3 First in ClinVar: Feb 13, 2023 Last updated: Feb 20, 2024	Publications: PubMed (1) PubMed: 24482476 Comment: This sequence change creates a premature translational stop signal (p.Lys385Glufs16) in the NT5C2 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Lys385Glufs16) in the NT5C2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NT5C2 are known to be pathogenic (PMID: 24482476). This variant is present in population databases (rs769417998, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with NT5C2-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Lys385Glufs*16) in the NT5C2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NT5C2 are known to be pathogenic (PMID: 24482476). This variant is present in population databases (rs769417998, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with NT5C2-related conditions. For these reasons, this variant has been classified as Pathogenic.

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
Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.	Novarino G	Science (New York, N.Y.)	2014	PMID: 24482476

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_001351169.2(NT5C2):c.1153_1154del (p.Lys385fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...