NM_001111125.3(IQSEC2):c.4434_4438dup (p.Lys1480fs) AND Intellectual disability, X-linked 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 31, 2017
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:: RCV000547957.6

Allele description [Variation Report for NM_001111125.3(IQSEC2):c.4434_4438dup (p.Lys1480fs)]

NM_001111125.3(IQSEC2):c.4434_4438dup (p.Lys1480fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

Xp11.22

Genomic location:

Preferred name:

NM_001111125.3(IQSEC2):c.4434_4438dup (p.Lys1480fs)

HGVS:

NC_000023.11:g.53234249_53234253dup
NG_021296.2:g.92099_92103dup
NM_001111125.3:c.4434_4438dupMANE SELECT
NM_015075.2:c.*919_*923dup
NP_001104595.1:p.Lys1480fs
LRG_1194t1:c.4434_4438dup
LRG_1194:g.92099_92103dup
LRG_1194p1:p.Lys1480fs
NC_000023.10:g.53263429_53263430insTGGCC
NC_000023.10:g.53263431_53263435dup
NM_001111125.2:c.4434_4438dupGGCCA

Protein change:

K1480fs

Links:

dbSNP: rs1556858912

NCBI 1000 Genomes Browser:

rs1556858912

Molecular consequence:

NM_015075.2:c.*919_*923dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001111125.3:c.4434_4438dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000649587	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 31, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000649587

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 31, 2017)

germline

clinical testing

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	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

Details of each submission

From Invitae, SCV000649587.4

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

Description

Family studies have indicated that this variant was not present in the parents of an individual with clinical features consistent with an IQSEC2-related condition, which suggests that it was de novo in that affected individual (Invitae). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with IQSEC2-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change inserts 5 nucleotides in exon 15 of the IQSEC2 mRNA (c.4434_4438dupGGCCA), causing a frameshift at codon 1480 (p.Lys1480Argfs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acids and extend the length of the IQSEC2 protein by 7 additional amino acids.

#	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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