rs1559533185

Variant names:

• chr2-121530889-TTTC-T
• rs1559533185
• NM_001395891.1:c.196-567_196-565delGAA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-567_196-565delGAA variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000924 in 541,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 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.196-567_196-565delGAA		intron	N/A	NP_001382820.1	A0A8V8TLP7
	RNU4ATAC	NR_023343.3	MANE Select	n.13_15delCTT		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	NM_015282.3		c.196-567_196-565delGAA		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.196-567_196-565delGAA		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.13_15delCTT		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	ENST00000263710.8	TSL:5	c.196-567_196-565delGAA		intron	N/A	ENSP00000263710.4	Q7Z460-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000231 AC: 3 AN: 129674 AF XY: 0.0000282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000607

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000924 AC: 5 AN: 541284 Hom.: 0 AF XY: 0.0000103 AC XY: 3 AN XY: 292000

African (AFR) AF: 0.00 AC: 0 AN: 15582

American (AMR) AF: 0.00 AC: 0 AN: 34414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19918

East Asian (EAS) AF: 0.00 AC: 0 AN: 31896

South Asian (SAS) AF: 0.00 AC: 0 AN: 62446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2424

European-Non Finnish (NFE) AF: 0.0000161 AC: 5 AN: 311420

Other (OTH) AF: 0.00 AC: 0 AN: 30058

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

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: rs1559533185; hg19: chr2-122288465;