VCV001763088.2 - ClinVar

NM_003924.4(PHOX2B):c.836_843del (p.Pro279fs)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003924.4(PHOX2B):c.836_843del (p.Pro279fs)

Variation ID: 1763088 Accession: VCV001763088.2

Type and length

Deletion, 8 bp

Location

Cytogenetic: 4p13 4: 41745909-41745916 (GRCh38) [ NCBI UCSC ] 4: 41747926-41747933 (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	Nov 29, 2022	May 1, 2024	Oct 25, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_003924.4:c.836_843del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003915.2:p.Pro279fs	frameshift
NM_003924.3:c.836_843delCCATCACC		frameshift
NC_000004.12:g.41745911_41745918del
NC_000004.11:g.41747928_41747935del
NG_008243.1:g.8055_8062del
NG_053075.1:g.37_44del
LRG_513:g.8055_8062del
LRG_513t1:c.834_841del	LRG_513p1:p.Pro279Leufs

... more HGVS ... less HGVS

Protein change

P279fs

Other names

Canonical SPDI

NC_000004.12:41745908:GGTGATGGGG:GG

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.
PHOX2B		-	-	GRCh38 GRCh37	772	1118

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.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Oct 25, 2016	RCV002434748.2

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 (Oct 25, 2016)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002678576.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: The c.836_843delCCATCACC pathogenic mutation, located in coding exon 3 of the PHOX2B gene, results from a deletion of 8 nucleotides at nucleotide positions 836 to … (more) The c.836_843delCCATCACC pathogenic mutation, located in coding exon 3 of the PHOX2B gene, results from a deletion of 8 nucleotides at nucleotide positions 836 to 843, causing a translational frameshift with a predicted alternate stop codon. This alteration has been identified in an infant with congenital central hypoventilation syndrome (CCHS) presenting with Hirschprung syndrome and a neural crest tumor (internal data). Frameshifts are typically deleterious in nature, and although the alteration is not expected to trigger nonsense-mediated mRNA decay due to its location, it is predicted to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. (less)

Comment:

The c.836_843delCCATCACC pathogenic mutation, located in coding exon 3 of the PHOX2B gene, results from a deletion of 8 nucleotides at nucleotide positions 836 to 843, causing a translational frameshift with a predicted alternate stop codon. This alteration has been identified in an infant with congenital central hypoventilation syndrome (CCHS) presenting with Hirschprung syndrome and a neural crest tumor (internal data). Frameshifts are typically deleterious in nature, and although the alteration is not expected to trigger nonsense-mediated mRNA decay due to its location, it is predicted to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.

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 01, 2024

ClinVar Genomic variation as it relates to human health

NM_003924.4(PHOX2B):c.836_843del (p.Pro279fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...