chr2-121530892-C-T

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 8P and 2B. PP5_Very_StrongBP4BS2_Supporting

The NM_001395891.1(CLASP1):c.196-567G>A variant causes a intron change. The variant allele was found at a frequency of 0.000497 in 693,814 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: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

CLASP1
NM_001395891.1 intron

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:16U:1

Conservation

PhyloP100: 5.71

Publications

6 publications found

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]

CLASP1 links:

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]

RNU4ATAC links:

CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

CLASP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PP5

Variant 2-121530892-C-T is Pathogenic according to our data. Variant chr2-121530892-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 218083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.2). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAd4 at 56 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASP1	NM_001395891.1	MANE Select	c.196-567G>A	intron	N/A	NP_001382820.1	A0A8V8TLP7
RNU4ATAC	NR_023343.3	MANE Select	n.13C>T	non_coding_transcript_exon	Exon 1 of 1
CLASP1	NM_015282.3		c.196-567G>A	intron	N/A	NP_056097.1	Q7Z460-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASP1	ENST00000696935.1	MANE Select	c.196-567G>A	intron	N/A	ENSP00000512981.1	A0A8V8TLP7
RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.13C>T	non_coding_transcript_exon	Exon 1 of 1
CLASP1	ENST00000263710.8	TSL:5	c.196-567G>A	intron	N/A	ENSP00000263710.4	Q7Z460-1

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000347

AC:

AN:

129764

AF XY:

0.000353

show subpopulations

Gnomad AFR exome

AF:

0.000329

Gnomad AMR exome

AF:

0.000332

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000962

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000465

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000534

AC:

289

AN:

541512

Hom.:

Cov.:

AF XY:

0.000568

AC XY:

166

AN XY:

292136

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

15596

American (AMR)

AF:

0.000320

AC:

AN:

34428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19918

East Asian (EAS)

AF:

0.000251

AC:

AN:

31892

South Asian (SAS)

AF:

0.000496

AC:

AN:

62448

European-Finnish (FIN)

AF:

0.000151

AC:

AN:

33128

Middle Eastern (MID)

AF:

0.000412

AC:

AN:

2426

European-Non Finnish (NFE)

AF:

0.000674

AC:

210

AN:

311586

Other (OTH)

AF:

0.000565

AC:

AN:

30090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000368

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000359

Hom.:

Bravo

AF:

0.000393

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Pathogenic/Likely pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Roifman syndrome (9)

not provided (6)

CLASP1-related disorder (1)

Lowry-Wood syndrome;C1846059:Roifman syndrome;C1859452:Osteodysplastic primordial dwarfism, type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

5.7

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over