rs7374396

Positions:

• chr3-33628852-C-A

Variant summary

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

The NM_001365631.1(CLASP2):​c.943-1772G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,910 control chromosomes in the GnomAD database, including 3,988 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 0.22 (3988 hom., cov: 31)
• Consequence: CLASP2 NM_001365631.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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]

CLASP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLASP2	NM_001365631.1	c.943-1772G>T		intron_variant		ENST00000682230.1	NP_001352560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLASP2	ENST00000682230.1	c.943-1772G>T		intron_variant			NM_001365631.1	ENSP00000507498.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32963 AN: 151790 Hom.: 3974 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.217 AC: 32997 AN: 151910 Hom.: 3988 Cov.: 31 AF XY: 0.221 AC XY: 16386 AN XY: 74228

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.234

Alfa AF: 0.236 Hom.: 5860

Bravo AF: 0.222

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.44

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: rs7374396; hg19: chr3-33670344;