VCV001343173.6 - ClinVar

NM_006180.6(NTRK2):c.370C>T (p.Arg124Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance

2 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_006180.6(NTRK2):c.370C>T (p.Arg124Ter)

Variation ID: 1343173 Accession: VCV001343173.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q21.33 9: 84707854 (GRCh38) [ NCBI UCSC ] 9: 87322769 (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	Mar 12, 2022	Apr 13, 2025	Nov 27, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_006180.6:c.370C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006171.2:p.Arg124Ter	nonsense
NM_001007097.3:c.370C>T	NP_001007098.1:p.Arg124Ter	nonsense
NM_001018064.3:c.370C>T	NP_001018074.1:p.Arg124Ter	nonsense
NM_001018065.2:c.370C>T	NP_001018075.1:p.Arg124Ter	nonsense
NM_001018066.3:c.370C>T	NP_001018076.1:p.Arg124Ter	nonsense
NM_001291937.2:c.370C>T	NP_001278866.1:p.Arg124Ter	nonsense
NM_001369532.1:c.370C>T	NP_001356461.1:p.Arg124Ter	nonsense
NM_001369533.1:c.370C>T	NP_001356462.1:p.Arg124Ter	nonsense
NM_001369534.1:c.370C>T	NP_001356463.1:p.Arg124Ter	nonsense
NM_001369535.1:c.-99C>T		5 prime UTR
NM_001369536.1:c.-99C>T		5 prime UTR
NM_001369537.1:c.370C>T	NP_001356466.1:p.Arg124Ter	nonsense
NM_001369538.1:c.370C>T	NP_001356467.1:p.Arg124Ter	nonsense
NM_001369539.1:c.370C>T	NP_001356468.1:p.Arg124Ter	nonsense
NM_001369540.1:c.370C>T	NP_001356469.1:p.Arg124Ter	nonsense
NM_001369541.1:c.370C>T	NP_001356470.1:p.Arg124Ter	nonsense
NM_001369542.1:c.370C>T	NP_001356471.1:p.Arg124Ter	nonsense
NM_001369543.1:c.370C>T	NP_001356472.1:p.Arg124Ter	nonsense
NM_001369544.1:c.370C>T	NP_001356473.1:p.Arg124Ter	nonsense
NM_001369545.1:c.370C>T	NP_001356474.1:p.Arg124Ter	nonsense
NM_001369546.1:c.370C>T	NP_001356475.1:p.Arg124Ter	nonsense
NM_001369547.1:c.370C>T	NP_001356476.1:p.Arg124Ter	nonsense
NM_001369548.1:c.370C>T	NP_001356477.1:p.Arg124Ter	nonsense
NM_001369549.1:c.370C>T	NP_001356478.1:p.Arg124Ter	nonsense
NM_001369550.1:c.-99C>T		5 prime UTR
NM_001369551.1:c.-99C>T		5 prime UTR
NM_001369552.1:c.-99C>T		5 prime UTR
NC_000009.12:g.84707854C>T
NC_000009.11:g.87322769C>T
NG_012201.2:g.44304C>T

... more HGVS ... less HGVS

Protein change

R124*

Other names

Canonical SPDI

NC_000009.12:84707853:C:T

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: CA374005375 dbSNP: rs1229434307 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.
NTRK2		-	-	GRCh38 GRCh37	801	856

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 disorder	Uncertain significance (1)	criteria provided, single submitter	Feb 18, 2021	RCV001843774.2
not provided	Uncertain significance (1)	criteria provided, single submitter	Nov 27, 2023	RCV002543281.4

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 (Feb 18, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Developmental disorder	Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine Accession: SCV002102913.2 First in ClinVar: Mar 12, 2022 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: paternal Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: paternal Affected status: yes Sex: male

Uncertain significance (Nov 27, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003235934.3 First in ClinVar: Feb 07, 2023 Last updated: Feb 25, 2025	Comment: show This sequence change creates a premature translational stop signal (p.Arg124*) in the NTRK2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NTRK2 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NTRK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1343173). 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change creates a premature translational stop signal (p.Arg124*) in the NTRK2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NTRK2 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NTRK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1343173). 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.

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 rs1229434307 ...

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 Apr 13, 2025