2-121530887-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_001395891.1(CLASP1):c.196-562G>T variant causes a intron change. The variant allele was found at a frequency of 0.00000555 in 540,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
CLASP1
NM_001395891.1 intron
NM_001395891.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.74
Genes affected
CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]
RNU4ATAC (HGNC:34016): (RNA, U4atac small nuclear) The small nuclear RNA (snRNA) encoded by this gene is part of the U12-dependent minor spliceosome complex. In addition to the encoded RNA, this ribonucleoprotein complex consists of U11, U12, U5, and U6atac snRNAs. The U12-dependent spliceosome acts on approximately 700 specific introns in the human genome. Defects in this gene are a cause of microcephalic osteodysplastic primordial dwarfism type 1 (MOPD). [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-121530887-C-A is Pathogenic according to our data. Variant chr2-121530887-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 692040.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-121530887-C-A is described in Lovd as [Pathogenic].
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.21). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLASP1 | NM_001395891.1 | c.196-562G>T | intron_variant | ENST00000696935.1 | NP_001382820.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLASP1 | ENST00000696935.1 | c.196-562G>T | intron_variant | NM_001395891.1 | ENSP00000512981.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD4 exome AF: 0.00000555 AC: 3AN: 540686Hom.: 0 Cov.: 0 AF XY: 0.0000103 AC XY: 3AN XY: 291572
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GnomAD4 genome Cov.: 32
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32
Bravo
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lowry-Wood syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 11, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | Jul 16, 2018 | This variant occurs in an element of major importance for splicing in Stem II of the snRNA molecule and is therefore predicted to disrupt minor intron splicing activity (PMID: 26522830). A different nucleotide change at this position was previously reported in a compound heterozygous change in a patient with Roifman Syndrome (PMID: 26522830). The variant is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. This variant was detected in trans with another CLASP1 variant classified as likely pathogenic. Based on the available evidence the variant is classified as Likely Pathogenic. - |
Computational scores
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Name
Calibrated prediction
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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