chrX-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):βc.4419delβ(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 (β β ). 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