NM_001111125.3(IQSEC2):c.2563C>T (p.Arg855Ter) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 6, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004019603.1

Allele description [Variation Report for NM_001111125.3(IQSEC2):c.2563C>T (p.Arg855Ter)]

NM_001111125.3(IQSEC2):c.2563C>T (p.Arg855Ter)

Gene:

IQSEC2:IQ motif and Sec7 domain ArfGEF 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.22

Genomic location:

Preferred name:

NM_001111125.3(IQSEC2):c.2563C>T (p.Arg855Ter)

HGVS:

NC_000023.11:g.53248133G>A
NG_021296.2:g.78218C>T
NM_001111125.1:c.2563C>T
NM_001111125.3:c.2563C>TMANE SELECT
NM_015075.2:c.1948C>T
NP_001104595.1:p.Arg855Ter
NP_055890.1:p.Arg650Ter
LRG_1194t1:c.2563C>T
LRG_1194:g.78218C>T
LRG_1194p1:p.Arg855Ter
NC_000023.10:g.53277315G>A
NM_001111125.2:c.2563C>T

Protein change:

R650*; ARG855TER

Links:

OMIM: 300522.0007; dbSNP: rs587777261

NCBI 1000 Genomes Browser:

rs587777261

Molecular consequence:

NM_001111125.3:c.2563C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015075.2:c.1948C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004889604	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 6, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23020937, 23674175 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004889604

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 6, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Citations

PubMed

Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Röpke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, et al.

Lancet. 2012 Nov 10;380(9854):1674-82. doi: 10.1016/S0140-6736(12)61480-9. Epub 2012 Sep 27.

PubMed [citation]

PMID:: 23020937

Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability.

Tran Mau-Them F, Willems M, Albrecht B, Sanchez E, Puechberty J, Endele S, Schneider A, Ruiz Pallares N, Missirian C, Rivier F, Girard M, Holder M, Manouvrier S, Touitou I, Lefort G, Sarda P, Moncla A, Drunat S, Wieczorek D, Genevieve D.

Eur J Hum Genet. 2014 Feb;22(2):289-92. doi: 10.1038/ejhg.2013.113. Epub 2013 May 15.

PubMed [citation]

PMID:: 23674175
PMCID:: PMC3895633

Details of each submission

From Ambry Genetics, SCV004889604.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.2563C>T (p.R855*) alteration, located in exon 7 (coding exon 7) of the IQSEC2 gene, consists of a C to T substitution at nucleotide position 2563. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 855. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in two individual with features consistent with IQSEC2-related neurodevelopmental disorder (Rauch, 2012; Tran Mau-Them, 2014; DECIPHER). Based on the available evidence, this alteration is classified as pathogenic.

#	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

Last Updated: Sep 29, 2024

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