Variant 3-33543517-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365631.1(CLASP2):c.3320C>T(p.Thr1107Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,611,652 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 24 hom. )

Consequence

CLASP2
NM_001365631.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.51

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007506788).

BP6

Variant 3-33543517-G-A is Benign according to our data. Variant chr3-33543517-G-A is described in ClinVar as [Benign]. Clinvar id is 3056625.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASP2	NM_001365631.1 linkuse as main transcript	c.3320C>T	p.Thr1107Ile	missense_variant	32/39	ENST00000682230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLASP2	ENST00000682230.1 linkuse as main transcript	c.3320C>T	p.Thr1107Ile	missense_variant	32/39		NM_001365631.1	P3

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

446

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00346

AC:

863

AN:

249226

Hom.:

AF XY:

0.00354

AC XY:

479

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00467

Gnomad OTH exome

AF:

0.00562

GnomAD4 exome

AF:

0.00405

AC:

5906

AN:

1459376

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

2859

AN XY:

726242

show subpopulations

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00209

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.00428

Gnomad4 OTH exome

AF:

0.00561

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152276

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00416

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00464

Hom.:

Bravo

AF:

0.00308

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.00522

AC:

ExAC

AF:

0.00353

AC:

426

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00610

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CLASP2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D;D;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0075

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.3

N;N;.;N;N;.

REVEL

Benign

0.28

Sift

Benign

0.059

T;T;.;T;T;.

Sift4G

Benign

0.063

T;T;T;T;T;T

Polyphen

0.24

.;B;.;.;.;.

Vest4

0.32

MVP

0.29

MPC

1.2

ClinPred

0.019

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)

0.020

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