X-53234266-TG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_StrongPP5_Very_Strong
The NM_001111125.3(IQSEC2):c.4419del(p.Ser1474ValfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 829,857 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P1473P) has been classified as Likely benign.
Frequency
Consequence
NM_001111125.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IQSEC2 | NM_001111125.3 | c.4419del | p.Ser1474ValfsTer21 | frameshift_variant | 15/15 | ENST00000642864.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IQSEC2 | ENST00000642864.1 | c.4419del | p.Ser1474ValfsTer21 | frameshift_variant | 15/15 | NM_001111125.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 15
GnomAD3 exomes AF: 0.000180 AC: 9AN: 50130Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 8622
GnomAD4 exome AF: 0.0000265 AC: 22AN: 829857Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 235173
GnomAD4 genome ? Cov.: 15
ClinVar
Submissions by phenotype
Intellectual disability, X-linked 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Feb 15, 2018 | PVS1, PS2; This variant introduces a single-base-pair deletion in the coding sequence of the IQSEC2 gene, which leads to a shift in the protein reading frame and introduces of a premature termination codon in a gene where loss of function is a known mechanism of disease [ACMG: PVS1]. Sanger sequencing confirmed this to be a de novo alteration, as it was not detected in the submitted parental specimens (identity confirmed)[ACMG: PS2]. No evidence was found to support any of the ACMG Benign criteria; therefore, this alteration meets ACMG guidelines for classification as a pathogenic variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at