Variant 3-33517048-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001365631.1(CLASP2):c.3914T>G(p.Phe1305Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CLASP2
NM_001365631.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.53

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26025364).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASP2	NM_001365631.1 linkuse as main transcript	c.3914T>G	p.Phe1305Cys	missense_variant	35/39	ENST00000682230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLASP2	ENST00000682230.1 linkuse as main transcript	c.3914T>G	p.Phe1305Cys	missense_variant	35/39		NM_001365631.1	P3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249052

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461368

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726968

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2022

The c.3941T>G (p.F1314C) alteration is located in exon 36 (coding exon 36) of the CLASP2 gene. This alteration results from a T to G substitution at nucleotide position 3941, causing the phenylalanine (F) at amino acid position 1314 to be replaced by a cysteine (C). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

.;T;.;T;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.26

T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.8

N;N;.;N;N;.

REVEL

Benign

0.24

Sift

Benign

0.25

T;T;.;D;T;.

Sift4G

Uncertain

0.010

D;D;D;D;D;D

Polyphen

0.95

.;P;.;.;.;.

Vest4

0.63

MutPred

0.40

.;Gain of helix (P = 0.062);.;.;.;.;

MVP

0.21

MPC

1.6

ClinPred

0.83

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over