NM_001111125.3(IQSEC2):c.3307C>T (p.Arg1103Trp) AND Intellectual disability, X-linked 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 27, 2023
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:: RCV001044514.14

Allele description

NM_001111125.3(IQSEC2):c.3307C>T (p.Arg1103Trp)

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.3307C>T (p.Arg1103Trp)

HGVS:

NC_000023.11:g.53236466G>A
NG_021296.2:g.89885C>T
NM_001111125.3:c.3307C>TMANE SELECT
NM_015075.2:c.2692C>T
NP_001104595.1:p.Arg1103Trp
NP_055890.1:p.Arg898Trp
LRG_1194t1:c.3307C>T
LRG_1194:g.89885C>T
LRG_1194p1:p.Arg1103Trp
NC_000023.10:g.53265648G>A
NM_001111125.2:c.3307C>T

Protein change:

R1103W

Links:

dbSNP: rs868950692

NCBI 1000 Genomes Browser:

rs868950692

Molecular consequence:

NM_001111125.3:c.3307C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015075.2:c.2692C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, X-linked 1 (XLID1)
Synonyms:: Mental retardation, X-linked, nonspecific; Atkin Flaitz Patil Smith syndrome; MENTAL RETARDATION, X-LINKED 18; See all synonyms [MedGen]
Identifiers:: Gene: 170530; MONDO: MONDO:0010656; MedGen: C2931498; Orphanet: 777; OMIM: 309530

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Homo sapiens protein kinase cAMP-activated catalytic subunit beta (PRKACB), tran...
Homo sapiens protein kinase cAMP-activated catalytic subunit beta (PRKACB), transcript variant 8, mRNA
gi|1890275789|ref|NM_001242861.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001208315	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 21, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003920767	Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL)	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 27, 2023)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001208315

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 21, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003920767

Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL)

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 27, 2023)

germline

research

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV001208315.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with IQSEC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 1103 of the IQSEC2 protein (p.Arg1103Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan.

#	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 Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), SCV003920767.1

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

Last Updated: May 19, 2024

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