NM_001365631.1:c.4162C>A

Variant names:

• chr3-33510713-G-T
• rs906936375
• NM_001365631.1:c.4162C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365631.1(CLASP2):​c.4162C>A​(p.Pro1388Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 6.53
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

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.4162C>A	p.Pro1388Thr	missense	Exon 37 of 39	NP_001352560.1	A0A804HJG7
	CLASP2	NM_001365628.1		c.4249C>A	p.Pro1417Thr	missense	Exon 38 of 40	NP_001352557.1
	CLASP2	NM_001365629.1		c.4246C>A	p.Pro1416Thr	missense	Exon 38 of 40	NP_001352558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	ENST00000682230.1	MANE Select	c.4162C>A	p.Pro1388Thr	missense	Exon 37 of 39	ENSP00000507498.1	A0A804HJG7
	CLASP2	ENST00000468888.6	TSL:5	c.4186C>A	p.Pro1396Thr	missense	Exon 37 of 39	ENSP00000419974.2	E7EW49
	CLASP2	ENST00000399362.8	TSL:5	c.4183C>A	p.Pro1395Thr	missense	Exon 37 of 39	ENSP00000382297.4	E7ERI8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.28	T
PhyloP100		6.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.78
MutPred		0.61		Gain of ubiquitination at K1400 (P = 0.1378)
MVP		0.68
MPC		1.4
ClinPred		0.98	D
GERP RS		6.1
Mutation Taster		=57/43	polymorphism

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: rs906936375; hg19: chr3-33552205;