VCV003236619.1 - ClinVar

NM_004247.4(EFTUD2):c.2562-2A>G

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004247.4(EFTUD2):c.2562-2A>G

Variation ID: 3236619 Accession: VCV003236619.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 44852564 (GRCh38) [ NCBI UCSC ] 17: 42929932 (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	May 27, 2024	May 26, 2024	Feb 8, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004247.4:c.2562-2A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor
NM_001142605.2:c.2457-2A>G		splice acceptor
NM_001258353.2:c.2562-2A>G		splice acceptor
NM_001258354.2:c.2532-2A>G		splice acceptor
NC_000017.11:g.44852564T>C
NC_000017.10:g.42929932T>C
NG_032674.1:g.52062A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:44852563:T:C

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.
EFTUD2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	682	695

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.
Mandibulofacial dysostosis-microcephaly syndrome	Likely pathogenic (1)	criteria provided, single submitter	Feb 8, 2024	RCV004556002.1

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 (Feb 08, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mandibulofacial dysostosis-microcephaly syndrome Affected status: yes Allele origin: germline	Clinical Genomics Laboratory, Washington University in St. Louis Accession: SCV005045144.1 First in ClinVar: May 26, 2024 Last updated: May 26, 2024	Comment: The EFTUD2 c.2562-2A>G variant, to our knowledge, has not been reported in the medical literature. This variant is absent from the general population (gnomAD v.2.1.1), … (more) The EFTUD2 c.2562-2A>G variant, to our knowledge, has not been reported in the medical literature. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant occurs within the canonical splice acceptor site, which is predicted to cause skipping of the exon, leading to an out of frame transcript. Additionally, another variant in the same nucleotide, c.2562-2del, has been described as occurring de novo in multiple affected individuals and is considered pathogenic (Lehalle D et al., PMID: 24470203). Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic. (less)

Comment:

The EFTUD2 c.2562-2A>G variant, to our knowledge, has not been reported in the medical literature. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant occurs within the canonical splice acceptor site, which is predicted to cause skipping of the exon, leading to an out of frame transcript. Additionally, another variant in the same nucleotide, c.2562-2del, has been described as occurring de novo in multiple affected individuals and is considered pathogenic (Lehalle D et al., PMID: 24470203). Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely 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

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 27, 2024

ClinVar Genomic variation as it relates to human health

NM_004247.4(EFTUD2):c.2562-2A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...