VCV003363164.2 - ClinVar

NM_013296.5(GPSM2):c.1337_1338del (p.Phe446fs)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_013296.5(GPSM2):c.1337_1338del (p.Phe446fs)

Variation ID: 3363164 Accession: VCV003363164.2

Type and length

Deletion, -

Location

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 27, 2024	Nov 30, 2024	May 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_013296.5:c.1337_1338del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_037428.3:p.Phe446fs	frameshift
NM_001321038.2:c.1337_1338del	NP_001307967.1:p.Phe446fs	frameshift
NM_001321039.3:c.1337_1338del	NP_001307968.1:p.Phe446fs	frameshift
NM_013296.4:c.1337_1338del
NC_000001.11:g.108918686_108918687del
NC_000001.10:g.109461308_109461309del
NG_028108.2:g.48337_48338del
LRG_1373:g.48337_48338del
LRG_1373t1:c.1337_1338del	LRG_1373p1:p.Phe446fs

... more HGVS ... less HGVS

Protein change

F446fs

Other names

Canonical SPDI

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

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.
GPSM2		-	-	GRCh38 GRCh37	240	319

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.
Chudley-McCullough syndrome	Pathogenic (1)	no assertion criteria provided	Oct 16, 2024	RCV004765450.1
not provided	Likely pathogenic (1)	criteria provided, single submitter	May 22, 2024	RCV004794697.1

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.
Likely pathogenic (May 22, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005414957.1 First in ClinVar: Nov 30, 2024 Last updated: Nov 30, 2024	Comment: Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more) Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge (less)
Pathogenic (Oct 16, 2024)	no assertion criteria provided Method: clinical testing	Chudley-McCullough syndrome (Autosomal recessive inheritance) Affected status: yes Allele origin: unknown	CGC Genetics, Unilabs Accession: SCV005374867.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024	Comment: The variant NM_013296.5:c.1337_1338del p.(Phe446Cysfs16), detected in homozygosity in a proband with Chudley-McCullough syndrome, is not described in the literature. It is reported in the gnomAD … (more) The variant NM_013296.5:c.1337_1338del p.(Phe446Cysfs16), detected in homozygosity in a proband with Chudley-McCullough syndrome, is not described in the literature. It is reported in the gnomAD v2 population database (0.0011%, with 3 heterozygous individuals). It is a frameshift variant that introduces a premature stop codon, which in turn is predicted to lead to the creation of a truncated protein and/or a reduction in its expression due to mRNA degradation. With the information currently available, this should be classified as a pathogenic variant with the following ACMG criteria: PVS1, PM2_supporting, PM3_supporting. (less) Zygosity: Homozygote

Comment:

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge

Comment:

The variant NM_013296.5:c.1337_1338del p.(Phe446Cysfs*16), detected in homozygosity in a proband with Chudley-McCullough syndrome, is not described in the literature. It is reported in the gnomAD v2 population database (0.0011%, with 3 heterozygous individuals). It is a frameshift variant that introduces a premature stop codon, which in turn is predicted to lead to the creation of a truncated protein and/or a reduction in its expression due to mRNA degradation. With the information currently available, this should be classified as a pathogenic variant with the following ACMG criteria: PVS1, PM2_supporting, PM3_supporting.

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 Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NM_013296.5(GPSM2):c.1337_1338del (p.Phe446fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...