rs200629644
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001111125.3(IQSEC2):c.1449G>A(p.Pro483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,209,839 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 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 0.000054 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000045 ( 0 hom. 13 hem. )
Consequence
IQSEC2
NM_001111125.3 synonymous
NM_001111125.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.501
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant X-53251127-C-T is Benign according to our data. Variant chrX-53251127-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 390121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.501 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.1449G>A | p.Pro483= | synonymous_variant | 5/15 | ENST00000642864.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQSEC2 | ENST00000642864.1 | c.1449G>A | p.Pro483= | synonymous_variant | 5/15 | NM_001111125.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000537 AC: 6AN: 111684Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33882
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GnomAD3 exomes AF: 0.0000383 AC: 7AN: 182568Hom.: 0 AF XY: 0.0000296 AC XY: 2AN XY: 67464
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GnomAD4 exome AF: 0.0000446 AC: 49AN: 1098103Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 13AN XY: 363473
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GnomAD4 genome ? AF: 0.0000537 AC: 6AN: 111736Hom.: 0 Cov.: 23 AF XY: 0.0000589 AC XY: 2AN XY: 33944
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 18, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Intellectual disability, X-linked 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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