rs782399288
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001111125.3(IQSEC2):c.3753C>T(p.His1251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,165,685 control chromosomes in the GnomAD database, including 1 homozygotes. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 21)
Exomes 𝑓: 0.000027 ( 1 hom. 14 hem. )
Consequence
IQSEC2
NM_001111125.3 synonymous
NM_001111125.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.568
Genes affected
IQSEC2 (HGNC:29059): (IQ motif and Sec7 domain ArfGEF 2) This gene encodes a guanine nucleotide exchange factor for the ARF family of small GTP-binding proteins. The encoded protein is a component of the postsynaptic density at excitatory synapses, and may play a critical role in cytoskeletal and synaptic organization through the activation of selected ARF substrates including ARF1 and ARF6. Mutations in this gene have been implicated in nonsyndromic X-linked cognitive disability. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant X-53234933-G-A is Benign according to our data. Variant chrX-53234933-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.568 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQSEC2 | NM_001111125.3 | c.3753C>T | p.His1251= | synonymous_variant | 15/15 | ENST00000642864.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQSEC2 | ENST00000642864.1 | c.3753C>T | p.His1251= | synonymous_variant | 15/15 | NM_001111125.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000357 AC: 4AN: 111891Hom.: 0 Cov.: 21 AF XY: 0.0000587 AC XY: 2AN XY: 34085
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GnomAD3 exomes AF: 0.0000714 AC: 8AN: 112024Hom.: 0 AF XY: 0.000150 AC XY: 6AN XY: 39882
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GnomAD4 exome AF: 0.0000266 AC: 28AN: 1053794Hom.: 1 Cov.: 45 AF XY: 0.0000406 AC XY: 14AN XY: 344728
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GnomAD4 genome ? AF: 0.0000357 AC: 4AN: 111891Hom.: 0 Cov.: 21 AF XY: 0.0000587 AC XY: 2AN XY: 34085
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 19, 2015 | - - |
Intellectual disability, X-linked 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 01, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at