chr2-121530990-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_ModerateBP4BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-665C>T variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 700,064 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 Pathogenic (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CLASP1
NM_001395891.1 intron

Scores

2

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 7.60
Variant links:
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]
CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5
Variant 2-121530990-G-A is Pathogenic according to our data. Variant chr2-121530990-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 30181.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-121530990-G-A is described in Lovd as [Pathogenic]. Variant chr2-121530990-G-A is described in Lovd as [Pathogenic].
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29). . Strength limited to SUPPORTING due to the PP5.
BS2
High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLASP1NM_001395891.1 linkc.196-665C>T intron_variant Intron 2 of 40 ENST00000696935.1 NP_001382820.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLASP1ENST00000696935.1 linkc.196-665C>T intron_variant Intron 2 of 40 NM_001395891.1 ENSP00000512981.1 A0A8V8TLP7

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152040
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000383
AC:
5
AN:
130490
Hom.:
0
AF XY:
0.0000140
AC XY:
1
AN XY:
71230
show subpopulations
Gnomad AFR exome
AF:
0.000164
Gnomad AMR exome
AF:
0.000123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000201
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
7
AN:
548024
Hom.:
0
Cov.:
0
AF XY:
0.00000674
AC XY:
2
AN XY:
296754
show subpopulations
Gnomad4 AFR exome
AF:
0.000127
Gnomad4 AMR exome
AF:
0.0000576
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000947
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152040
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lowry-Wood syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 08, 2011- -
not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 06, 2025This variant occurs in the RNU4ATAC gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (rs763500364, gnomAD 0.02%). This variant has been observed in individual(s) with RNU4ATAC-related conditions (PMID: 21474760, 29265708; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 30181). Functional studies have shown that this variant disrupts ncRNA function (PMID: 21474760, 32628740) For these reasons, this variant has been classified as Pathogenic. -
Osteodysplastic primordial dwarfism, type 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 08, 2011- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
CADD
Benign
19
DANN
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763500364; hg19: chr2-122288566; API