rs575472572

Variant names:

• chr2-121530934-G-A
• rs575472572
• NM_001395891.1:c.196-609C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-121530934-G-A
• chr2-121530934-G-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 8P and 2B. PP5_Very_Strong BP4 BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-609C>T variant causes a intron change. The variant allele was found at a frequency of 0.0000885 in 700,406 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 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:7
• Conservation: PhyloP100: 4.82
• Publications: 4 publications found

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)

ACMG classification

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

• PP5: Variant 2-121530934-G-A is Pathogenic according to our data. Variant chr2-121530934-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 30179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26). . Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAd4 at 13 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	NM_001395891.1	MANE Select	c.196-609C>T		intron	N/A	NP_001382820.1	A0A8V8TLP7
	RNU4ATAC	NR_023343.3	MANE Select	n.55G>A		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	NM_015282.3		c.196-609C>T		intron	N/A	NP_056097.1	Q7Z460-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.196-609C>T		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.55G>A		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	ENST00000263710.8	TSL:5	c.196-609C>T		intron	N/A	ENSP00000263710.4	Q7Z460-1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000690 AC: 9 AN: 130516 AF XY: 0.0000702

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000603

Gnomad OTH exome AF: 0.000250

GnomAD4 exome AF: 0.0000894 AC: 49 AN: 548088 Hom.: 0 Cov.: 0 AF XY: 0.0000809 AC XY: 24 AN XY: 296784

African (AFR) AF: 0.00 AC: 0 AN: 15734

American (AMR) AF: 0.0000864 AC: 3 AN: 34708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20026

East Asian (EAS) AF: 0.00 AC: 0 AN: 32112

South Asian (SAS) AF: 0.000112 AC: 7 AN: 62682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33196

Middle Eastern (MID) AF: 0.000409 AC: 1 AN: 2444

European-Non Finnish (NFE) AF: 0.0000979 AC: 31 AN: 316774

Other (OTH) AF: 0.000230 AC: 7 AN: 30412

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74484

African (AFR) AF: 0.0000962 AC: 4 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000110

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
4	-	-	Osteodysplastic primordial dwarfism, type 1 (4)
2	-	-	Lowry-Wood syndrome;C1846059:Roifman syndrome;C1859452:Osteodysplastic primordial dwarfism, type 1 (2)
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=8/92	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs575472572; hg19: chr2-122288510;