rs1037744173
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_001111125.3(IQSEC2):c.643C>T(p.Pro215Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000019 ( 0 hom. 2 hem. )
Failed GnomAD Quality Control
Consequence
IQSEC2
NM_001111125.3 missense
NM_001111125.3 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 3.13
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19054875).
BP6
Variant X-53320481-G-A is Benign according to our data. Variant chrX-53320481-G-A is described in ClinVar as [Benign]. Clinvar id is 471276.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IQSEC2 | NM_001111125.3 | c.643C>T | p.Pro215Ser | missense_variant | 1/15 | ENST00000642864.1 | NP_001104595.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IQSEC2 | ENST00000642864.1 | c.643C>T | p.Pro215Ser | missense_variant | 1/15 | NM_001111125.3 | ENSP00000495726.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000190 AC: 2AN: 1051416Hom.: 0 Cov.: 31 AF XY: 0.00000583 AC XY: 2AN XY: 343300
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1051416
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
343300
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, X-linked 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 03, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;.
REVEL
Benign
Sift
Uncertain
.;D;.
Sift4G
Benign
.;T;.
Vest4
0.28
MutPred
Gain of phosphorylation at P215 (P = 0.0041);Gain of phosphorylation at P215 (P = 0.0041);Gain of phosphorylation at P215 (P = 0.0041);
MVP
0.28
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at