rs370715569

Variant names:

• chr2-121530887-C-A
• rs370715569
• NM_001395891.1:c.196-562G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-121530887-C-A
• chr2-121530887-C-G
• chr2-121530887-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

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
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 5.74
• Publications: 2 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 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 VariationId is 692040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21). . Strength limited to SUPPORTING due to the PP5.

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.196-562G>T		intron	N/A	NP_001382820.1
	RNU4ATAC	NR_023343.3	MANE Select	n.8C>A		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	NM_015282.3		c.196-562G>T		intron	N/A	NP_056097.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.196-562G>T		intron	N/A	ENSP00000512981.1
	RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.8C>A		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	ENST00000263710.8	TSL:5	c.196-562G>T		intron	N/A	ENSP00000263710.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000555 AC: 3 AN: 540686 Hom.: 0 Cov.: 0 AF XY: 0.0000103 AC XY: 3 AN XY: 291572

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

American (AMR) AF: 0.00 AC: 0 AN: 34392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19912

East Asian (EAS) AF: 0.00 AC: 0 AN: 31890

South Asian (SAS) AF: 0.0000160 AC: 1 AN: 62428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2418

European-Non Finnish (NFE) AF: 0.00000643 AC: 2 AN: 310918

Other (OTH) AF: 0.00 AC: 0 AN: 30024

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Lowry-Wood syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		5.7
Mutation Taster		=0/100	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: rs370715569; hg19: chr2-122288463;