VCV002430934.2 - ClinVar

NM_014847.4(UBAP2L):c.3168+3A>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.

(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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_014847.4(UBAP2L):c.3168+3A>G

Variation ID: 2430934 Accession: VCV002430934.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q21.3 1: 154268957 (GRCh38) [ NCBI UCSC ] 1: 154241433 (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 5, 2023	Sep 3, 2023	Sep 30, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_014847.4:c.3168+3A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001287816.1:c.3198+3A>G		intron variant
NM_001330730.1:c.3201+3A>G		intron variant
NM_001375612.1:c.3201+3A>G		intron variant
NM_001375614.1:c.3168+3A>G		intron variant
NM_001375615.1:c.3165+3A>G		intron variant
NM_001375616.1:c.3165+3A>G		intron variant
NM_001375617.1:c.3198+3A>G		intron variant
NM_001375618.1:c.3168+3A>G		intron variant
NM_001375619.1:c.3168+3A>G		intron variant
NM_001375620.1:c.3165+3A>G		intron variant
NM_001375621.1:c.3165+3A>G		intron variant
NM_001375622.1:c.3165+3A>G		intron variant
NM_001375623.1:c.3168+3A>G		intron variant
NM_001375624.1:c.3165+3A>G		intron variant
NM_001375625.1:c.3201+3A>G		intron variant
NM_001375626.1:c.3168+3A>G		intron variant
NM_001375627.1:c.3168+3A>G		intron variant
NM_001375628.1:c.3165+3A>G		intron variant
NC_000001.11:g.154268957A>G
NC_000001.10:g.154241433A>G
NG_007369.1:g.1395A>G
LRG_64:g.1395A>G

... more HGVS ... less HGVS

Protein change

Other names

IVS26DS, A-G, +3

Canonical SPDI

NC_000001.11:154268956:A:G

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

OMIM: 616472.0005 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.
UBAP2L		-	-	GRCh38 GRCh37	59	77

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.
not provided	Pathogenic (1)	criteria provided, single submitter	Sep 30, 2022	RCV003129467.4
Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies	Pathogenic (1)	no assertion criteria provided	Aug 30, 2023	RCV003325321.3

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 (Sep 30, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV003806096.1 First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023	Comment: Published functional studies demonstrate a damaging effect due to impaired splicing (Jia X et al., 2022); Not observed at significant frequency in large population cohorts … (more) Published functional studies demonstrate a damaging effect due to impaired splicing (Jia X et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35977029) (less)
Pathogenic (Aug 30, 2023)	no assertion criteria provided Method: literature only	NEURODEVELOPMENTAL DISORDER WITH IMPAIRED LANGUAGE, BEHAVIORAL ABNORMALITIES, AND DYSMORPHIC FACIES Affected status: not provided Allele origin: germline	OMIM Accession: SCV004031260.1 First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023	Publications: PubMed (1) PubMed: 35977029 Comment on evidence: In a 6-year-old Caucasian girl (P12) with neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF; 620494), Jia et al. (2022) identified a … (more) In a 6-year-old Caucasian girl (P12) with neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF; 620494), Jia et al. (2022) identified a de novo heterozygous intronic A-to-G transition in the UBAP2L gene (c.3168+3A-G, NM_014847.4), resulting in the skipping of exon 26 and an in-frame deletion (Gln991_Gln1056del) at the C terminus. The mutation, which was found by trio-based whole-exome sequencing, was not present in the gnomAD database. UBAP2L-null HeLa cells transfected with the mutation showed significantly fewer stress granules under oxidative stress compared to controls. The patient had poor overall growth, short stature, speech regression, and generalized epilepsy. (less)

Comment:

Published functional studies demonstrate a damaging effect due to impaired splicing (Jia X et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35977029)

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
De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders.	Jia X	Science advances	2022	PMID: 35977029

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_014847.4(UBAP2L):c.3168+3A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...