NM_001111125.3(IQSEC2):c.2460-2A>G AND Intellectual disability, X-linked 1

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

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 26, 2022
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:: RCV000806617.4

Allele description

NM_001111125.3(IQSEC2):c.2460-2A>G

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.2460-2A>G

HGVS:

NC_000023.11:g.53248238T>C
NG_021296.2:g.78113A>G
NM_001111125.3:c.2460-2A>GMANE SELECT
NM_001410736.1:c.2460-2A>G
NM_015075.2:c.1845-2A>G
LRG_1194t1:c.2460-2A>G
LRG_1194:g.78113A>G
NC_000023.10:g.53277420T>C
NM_001111125.2:c.2460-2A>G

Links:

dbSNP: rs1602279457

NCBI 1000 Genomes Browser:

rs1602279457

Molecular consequence:

NM_001111125.3:c.2460-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001410736.1:c.2460-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_015075.2:c.1845-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Recent activity

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dedicator of cytokinesis protein 1 isoform X2 [Callithrix jacchus]
dedicator of cytokinesis protein 1 isoform X2 [Callithrix jacchus]
gi|1864421576|ref|XP_035125363.1|

Protein
hypothetical protein [Serratia sp. FGI94]
hypothetical protein [Serratia sp. FGI94]
gi|505488845|ref|WP_015673491.1|

Protein
choline-phosphate cytidylyltransferase B isoform X1 [Chelonia mydas]
choline-phosphate cytidylyltransferase B isoform X1 [Chelonia mydas]
gi|1561658179|ref|XP_027688499.1|

Protein
AbrB/MazE/SpoVT family DNA-binding domain-containing protein [Sulfolobus acidoca...
AbrB/MazE/SpoVT family DNA-binding domain-containing protein [Sulfolobus acidocaldarius]
gi|499598026|ref|WP_011278760.1|

Protein
glutathione S-transferase family protein [Cereibacter sphaeroides]
glutathione S-transferase family protein [Cereibacter sphaeroides]
gi|506403437|ref|WP_015923156.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000946625	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 21686261, 26793055, 27665735, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000946625

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 26, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability.

Shoubridge C, Walikonis RS, Gécz J, Harvey RJ.

Small GTPases. 2010 Sep;1(2):98-103.

PubMed [citation]

PMID:: 21686261
PMCID:: PMC3116596

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000946625.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant has not been reported in the literature in individuals affected with IQSEC2-related conditions. This sequence change affects an acceptor splice site in intron 6 of the IQSEC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IQSEC2 are known to be pathogenic (PMID: 21686261, 26793055, 27665735). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 651293). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: May 19, 2024

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