X-155298927-T-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_001289.6(CLIC2):c.168-17A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000748 in 1,203,626 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000027 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )
Consequence
CLIC2
NM_001289.6 intron
NM_001289.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.15
Genes affected
CLIC2 (HGNC:2063): (chloride intracellular channel 2) This gene encodes a chloride intracellular channel protein. Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. This protein plays a role in inhibiting the function of ryanodine receptor 2. A mutation in this gene is the cause of an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant X-155298927-T-A is Benign according to our data. Variant chrX-155298927-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2637799.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLIC2 | ENST00000369449.7 | c.168-17A>T | intron_variant | Intron 2 of 5 | 1 | NM_001289.6 | ENSP00000358460.2 | |||
CLIC2 | ENST00000321926.4 | c.167+109A>T | intron_variant | Intron 2 of 3 | 3 | ENSP00000318558.4 | ||||
CLIC2 | ENST00000465553.5 | n.283-17A>T | intron_variant | Intron 2 of 6 | 3 | |||||
CLIC2 | ENST00000491205.1 | n.222-17A>T | intron_variant | Intron 3 of 5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000269 AC: 3AN: 111475Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33665
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GnomAD3 exomes AF: 0.0000218 AC: 4AN: 183128Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67784
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GnomAD4 exome AF: 0.00000549 AC: 6AN: 1092151Hom.: 0 Cov.: 29 AF XY: 0.00000280 AC XY: 1AN XY: 357721
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GnomAD4 genome AF: 0.0000269 AC: 3AN: 111475Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33665
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 18, 2023 | Variant summary: CLIC2 c.168-17A>T alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.2e-05 in 183128 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.168-17A>T in individuals affected with X-Linked Intellectual Disability-Cardiomegaly Heart Failure Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. - |
Computational scores
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Name
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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