3-33551080-T-G

Variant names:

• chr3-33551080-T-G
• rs12487660
• NM_001365631.1:c.3153+172A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365631.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	NM_001365631.1	MANE Select	c.3153+172A>C		intron	N/A	NP_001352560.1
	CLASP2	NM_001365628.1		c.3240+172A>C		intron	N/A	NP_001352557.1
	CLASP2	NM_001365629.1		c.3237+172A>C		intron	N/A	NP_001352558.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	ENST00000682230.1	MANE Select	c.3153+172A>C		intron	N/A	ENSP00000507498.1
	CLASP2	ENST00000468888.6	TSL:5	c.3177+172A>C		intron	N/A	ENSP00000419974.2
	CLASP2	ENST00000399362.8	TSL:5	c.3174+172A>C		intron	N/A	ENSP00000382297.4

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

African (AFR) AF: 0.147 AC: 6123 AN: 41540

American (AMR) AF: 0.389 AC: 5948 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1500 AN: 5182

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4814

European-Finnish (FIN) AF: 0.292 AC: 3082 AN: 10564

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20529 AN: 67956

Other (OTH) AF: 0.291 AC: 615 AN: 2114

Alfa AF: 0.290 Hom.: 3510

Bravo AF: 0.270

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.57
DANN	Benign	0.57
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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