rs12487660

Positions:

• chr3-33551080-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365631.1(CLASP2):​c.3153+172A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,118 control chromosomes in the GnomAD database, including 5,986 homozygotes. 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: 𝑓 0.27 (5986 hom., cov: 32)
• Consequence: CLASP2 NM_001365631.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

CLASP2 (HGNC:17078): (cytoplasmic linker associated protein 2) Enables cytoskeletal protein binding activity; dystroglycan binding activity; and protein tyrosine kinase binding activity. Involved in several processes, including microtubule cytoskeleton organization; positive regulation of extracellular matrix organization; and regulation of supramolecular fiber organization. Located in several cellular components, including basal cortex; cortical microtubule plus-end; and ruffle membrane. Colocalizes with focal adhesion; kinetochore; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASP2	NM_001365631.1	c.3153+172A>C		intron_variant		ENST00000682230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLASP2	ENST00000682230.1	c.3153+172A>C		intron_variant			NM_001365631.1	P3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40351 AN: 152000 Hom.: 5971 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40383 AN: 152118 Hom.: 5986 Cov.: 32 AF XY: 0.267 AC XY: 19882 AN XY: 74374

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.291

Alfa AF: 0.289 Hom.: 3115

Bravo AF: 0.270

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.57
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs12487660; hg19: chr3-33592572; COSMIC: COSV56276262; COSMIC: COSV56276262;