3-33510711-TGG-CGT

Variant names:

• chr3-33510711-TGG-CGT
• NM_001365631.1:c.4162_4164delCCAinsACG
• CLASP2 p.Pro1388Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001365631.1(CLASP2):​c.4162_4164delCCAinsACG​(p.Pro1388Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1388S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLASP2 NM_001365631.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.63
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	NM_001365631.1	MANE Select	c.4162_4164delCCAinsACG	p.Pro1388Thr	missense	N/A	NP_001352560.1	A0A804HJG7
	CLASP2	NM_001365628.1		c.4249_4251delCCAinsACG	p.Pro1417Thr	missense	N/A	NP_001352557.1
	CLASP2	NM_001365629.1		c.4246_4248delCCAinsACG	p.Pro1416Thr	missense	N/A	NP_001352558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	ENST00000682230.1	MANE Select	c.4162_4164delCCAinsACG	p.Pro1388Thr	missense	N/A	ENSP00000507498.1	A0A804HJG7
	CLASP2	ENST00000468888.6	TSL:5	c.4186_4188delCCAinsACG	p.Pro1396Thr	missense	N/A	ENSP00000419974.2	E7EW49
	CLASP2	ENST00000399362.8	TSL:5	c.4183_4185delCCAinsACG	p.Pro1395Thr	missense	N/A	ENSP00000382297.4	E7ERI8

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-33552203;