VCV001065356.5 - ClinVar

NM_152654.3(DAND5):c.396_397dup (p.Tyr133fs)

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.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(1)

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_152654.3(DAND5):c.396_397dup (p.Tyr133fs)

Variation ID: 1065356 Accession: VCV001065356.5

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 19p13.13 19: 12973453-12973454 (GRCh38) [ NCBI UCSC ] 19: 13084267-13084268 (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	Oct 30, 2021	Aug 18, 2023	Aug 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_152654.3:c.396_397dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_689867.1:p.Tyr133fs	frameshift
NC_000019.10:g.12973454CT[5]
NC_000019.9:g.13084268CT[5]

Protein change

Y133fs

Other names

Canonical SPDI

NC_000019.10:12973453:CTCTCTCT:CTCTCTCTCT

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: 609068.0001 dbSNP: rs768842269 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.
DAND5		-	-	GRCh38 GRCh37	12	38

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.
Heterotaxy	Likely pathogenic (1)	no assertion criteria provided	Apr 24, 2021	RCV001732154.2
not provided	Uncertain significance (1)	no assertion criteria provided	Aug 14, 2023	RCV001822873.3

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.
Likely pathogenic (Apr 24, 2021)	no assertion criteria provided Method: research	Heterotaxy Affected status: yes Allele origin: inherited	Pediatric Genetics Clinic, Sheba Medical Center Accession: SCV001572814.1 First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021	Number of individuals with the variant: 1 Clinical Features: Transposition of the great arteries (present) , Pulmonary valve stenosis (present) , Unbalanced atrioventricular canal defect (present) Secondary finding: no
Uncertain significance (Aug 14, 2023)	no assertion criteria provided Method: literature only	VARIANT OF UNKNOWN SIGNIFICANCE Affected status: not provided Allele origin: germline	OMIM Accession: SCV002072459.3 First in ClinVar: Feb 02, 2022 Last updated: Aug 18, 2023	Publications: PubMed (1) PubMed: 34215651 Comment on evidence: This variant is classified as a variant of unknown significance because its contribution to heterotaxy (see 306955) has not been confirmed. In a cohort of … (more) This variant is classified as a variant of unknown significance because its contribution to heterotaxy (see 306955) has not been confirmed. In a cohort of 30 Arab-Muslim Israeli children with atrial situs abnormalities and associated congenital heart defects, Bolkier et al. (2022) performed whole-exome sequencing and identified a girl who was homozygous for a 2-bp duplication (c.396_397dupCT, NM_152654.2) in the DAND5 gene, causing a frameshift predicted to result in a premature termination codon (Tyr133SerfsTer11). The mutation was not found in an in-house database of approximately 4,500 exomes but was present in 2 heterozygous carriers in the gnomAD database. The mutation status of the proband's consanguineous parents was not reported. The patient exhibited a harmonious pattern of isomerism, with right atrial isomerism, right bronchial isomerism, and right abdominal isomerism. Associated congenital heart defects included dextrocardia, unbalanced complete atrioventricular septal defect, transposition of the great arteries, severe pulmonic stenosis, right atrial appendage, patent ductus arteriosus, and infracardiac total anomalous pulmonary venous drainage. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.	Bolkier Y	Journal of medical genetics	2022	PMID: 34215651

Text-mined citations for rs768842269 ...

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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_152654.3(DAND5):c.396_397dup (p.Tyr133fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs768842269 ...