rs1556880235

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001111125.3(IQSEC2):​c.294C>T​(p.His98His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000775 in 1,162,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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., 0 hem., cov: 22)
Exomes 𝑓: 0.0000048 ( 0 hom. 0 hem. )

Consequence

IQSEC2
NM_001111125.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.458

Publications

0 publications found
Variant links:
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]
IQSEC2 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
  • intellectual disability, X-linked 1
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • X-linked complex neurodevelopmental disorder
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
  • non-syndromic X-linked intellectual disability
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
  • severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant X-53320830-G-A is Benign according to our data. Variant chrX-53320830-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 471270.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.458 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IQSEC2NM_001111125.3 linkc.294C>T p.His98His synonymous_variant Exon 1 of 15 ENST00000642864.1 NP_001104595.1 Q5JU85-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IQSEC2ENST00000642864.1 linkc.294C>T p.His98His synonymous_variant Exon 1 of 15 NM_001111125.3 ENSP00000495726.1 Q5JU85-2

Frequencies

GnomAD3 genomes
AF:
0.0000361
AC:
4
AN:
110816
Hom.:
0
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000375
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000279
AC:
3
AN:
107523
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000155
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000476
AC:
5
AN:
1051144
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
342584
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24853
American (AMR)
AF:
0.000144
AC:
4
AN:
27809
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18544
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27044
South Asian (SAS)
AF:
0.00
AC:
0
AN:
49672
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
37265
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4054
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
817683
Other (OTH)
AF:
0.0000226
AC:
1
AN:
44220
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000361
AC:
4
AN:
110862
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33296
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
30493
American (AMR)
AF:
0.000374
AC:
4
AN:
10692
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2626
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3454
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2586
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6026
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
212
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
52586
Other (OTH)
AF:
0.00
AC:
0
AN:
1516
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, X-linked 1 Benign:1
Jul 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
11
DANN
Benign
0.97
PhyloP100
0.46
PromoterAI
-0.085
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1556880235; hg19: chrX-53350028; API