chr2-121530879-T-G

Variant names:

• chr2-121530879-T-G
• rs111741835
• NM_001395891.1:c.196-554A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-554A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000296 in 539,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• 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]

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

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 Gene-Disease associations (from GenCC):

• microcephalic osteodysplastic primordial dwarfism type I

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• RNU4ATAC spectrum disorder

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia, Broad Center for Mendelian Genomics, Ambry Genetics
• Roifman syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Lowry-Wood syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High AC in GnomAdExome4 at 16 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.196-554A>C		intron	N/A	NP_001382820.1	A0A8V8TLP7
	CLASP1	NM_015282.3		c.196-554A>C		intron	N/A	NP_056097.1	Q7Z460-1
	CLASP1	NM_001378003.1		c.196-554A>C		intron	N/A	NP_001364932.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.196-554A>C		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	CLASP1	ENST00000263710.8	TSL:5	c.196-554A>C		intron	N/A	ENSP00000263710.4	Q7Z460-1
	CLASP1	ENST00000961911.1		c.196-554A>C		intron	N/A	ENSP00000631970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000309 AC: 4 AN: 129362 AF XY: 0.0000425

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000296 AC: 16 AN: 539776 Hom.: 0 Cov.: 0 AF XY: 0.0000481 AC XY: 14 AN XY: 290978

African (AFR) AF: 0.00 AC: 0 AN: 15520

American (AMR) AF: 0.00 AC: 0 AN: 34302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19886

East Asian (EAS) AF: 0.00 AC: 0 AN: 31856

South Asian (SAS) AF: 0.000256 AC: 16 AN: 62388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2416

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 310292

Other (OTH) AF: 0.00 AC: 0 AN: 29996

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.54
DANN	Benign	0.77
PhyloP100		-0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs111741835; hg19: chr2-122288455;