NM_006734.4(HIVEP2):c.2827C>T (p.Arg943Ter) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Dec 17, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001092448.33

Allele description [Variation Report for NM_006734.4(HIVEP2):c.2827C>T (p.Arg943Ter)]

NM_006734.4(HIVEP2):c.2827C>T (p.Arg943Ter)

Gene:

HIVEP2:HIVEP zinc finger 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q24.2

Genomic location:

Preferred name:

NM_006734.4(HIVEP2):c.2827C>T (p.Arg943Ter)

HGVS:

NC_000006.12:g.142771912G>A
NG_047004.1:g.178290C>T
NM_006734.4:c.2827C>TMANE SELECT
NP_006725.3:p.Arg943Ter
NC_000006.11:g.143093049G>A
NM_006734.3:c.2827C>T

Protein change:

R943*; ARG943TER

Links:

OMIM: 143054.0002; dbSNP: rs869312841

NCBI 1000 Genomes Browser:

rs869312841

Molecular consequence:

NM_006734.4:c.2827C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000266477	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 29, 2021)	germline	clinical testing	Citation Link,
SCV001248964	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (May 1, 2019)	germline	clinical testing	Citation Link,
SCV001587229	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26153216, 27003583, 28492532
SCV002818182	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004031326	Molecular Genetics laboratory, Necker Hospital	no assertion criteria provided	Pathogenic (Jan 29, 2019)	de novo	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Loss-of-function variants in HIVEP2 are a cause of intellectual disability.

Srivastava S, Engels H, Schanze I, Cremer K, Wieland T, Menzel M, Schubach M, Biskup S, Kreiß M, Endele S, Strom TM, Wieczorek D, Zenker M, Gupta S, Cohen J, Zink AM, Naidu S.

Eur J Hum Genet. 2016 Apr;24(4):556-61. doi: 10.1038/ejhg.2015.151. Epub 2015 Jul 8.

PubMed [citation]

PMID:: 26153216
PMCID:: PMC4929870

Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features.

Steinfeld H, Cho MT, Retterer K, Person R, Schaefer GB, Danylchuk N, Malik S, Wechsler SB, Wheeler PG, van Gassen KL, Terhal PA, Verhoeven VJ, van Slegtenhorst MA, Monaghan KG, Henderson LB, Chung WK.

Neurogenetics. 2016 Jul;17(3):159-64. doi: 10.1007/s10048-016-0479-z. Epub 2016 Mar 22.

PubMed [citation]

PMID:: 27003583
PMCID:: PMC4907844

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000266477.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense 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 in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26153216)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001248964.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001587229.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 224791). This premature translational stop signal has been observed in individual(s) with intellectual disability (PMID: 26153216). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg943*) in the HIVEP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HIVEP2 are known to be pathogenic (PMID: 27003583).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV002818182.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Molecular Genetics laboratory, Necker Hospital, SCV004031326.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 30, 2024

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