2-121530887-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP5 BP4 BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-562G>C variant causes a intron change. The variant allele was found at a frequency of 0.0000231 in 692,862 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1
• 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: Likely_benign. The variant received -1 ACMG points.

• PP5: Variant 2-121530887-C-G is Pathogenic according to our data. Variant chr2-121530887-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1944546.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23). . Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAdExome4 at 14 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.196-562G>C		intron	N/A	NP_001382820.1
	RNU4ATAC	NR_023343.3	MANE Select	n.8C>G		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	NM_015282.3		c.196-562G>C		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>C		intron	N/A	ENSP00000512981.1
	RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.8C>G		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	ENST00000263710.8	TSL:5	c.196-562G>C		intron	N/A	ENSP00000263710.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000154 AC: 2 AN: 129556 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000415

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000203

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000259 AC: 14 AN: 540686 Hom.: 0 Cov.: 0 AF XY: 0.0000240 AC XY: 7 AN XY: 291572

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

American (AMR) AF: 0.0000291 AC: 1 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: 0.0000641 AC: 4 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: 0.0000289 AC: 9 AN: 310918

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

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		5.7

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;