chr2-121363225-C-T

Variant names:

• chr2-121363225-C-T
• NM_001395891.1:c.4216G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395891.1(CLASP1):​c.4216G>A​(p.Ala1406Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.59

Genes affected

CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLASP1	NM_001395891.1	c.4216G>A	p.Ala1406Thr	missense_variant	Exon 38 of 41	ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1	c.4216G>A	p.Ala1406Thr	missense_variant	Exon 38 of 41		NM_001395891.1	ENSP00000512981.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4153G>A (p.A1385T) alteration is located in exon 37 (coding exon 36) of the CLASP1 gene. This alteration results from a G to A substitution at nucleotide position 4153, causing the alanine (A) at amino acid position 1385 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.092	T;.;.;T;.;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D;D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.5	L;.;.;L;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.9	.;N;.;N;N;.
REVEL	Uncertain	0.31
Sift	Benign	0.26	.;T;.;T;T;.
Sift4G	Benign	0.15	.;T;T;T;T;T
Polyphen		1.0	D;.;.;D;.;.
Vest4		0.67, 0.68, 0.80, 0.66, 0.69
MVP		0.78
MPC		1.2
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.15
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-122120801; COSMIC: COSV55318031; COSMIC: COSV55318031;