Variant 3-33501703-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001365631.1(CLASP2):c.4383G>A(p.Ala1461=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,613,370 control chromosomes in the GnomAD database, including 509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 19 hom., cov: 32)

Exomes 𝑓: 0.024 ( 490 hom. )

Consequence

CLASP2
NM_001365631.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.44

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 3-33501703-C-T is Benign according to our data. Variant chr3-33501703-C-T is described in ClinVar as [Benign]. Clinvar id is 3037568.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.43 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0156 (2376/152184) while in subpopulation SAS AF= 0.0288 (139/4822). AF 95% confidence interval is 0.0249. There are 19 homozygotes in gnomad4. There are 1102 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2376 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASP2	NM_001365631.1 linkuse as main transcript	c.4383G>A	p.Ala1461=	synonymous_variant	38/39	ENST00000682230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLASP2	ENST00000682230.1 linkuse as main transcript	c.4383G>A	p.Ala1461=	synonymous_variant	38/39		NM_001365631.1	P3

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2376

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00459

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0182

AC:

4531

AN:

249000

Hom.:

AF XY:

0.0193

AC XY:

2610

AN XY:

135068

show subpopulations

Gnomad AFR exome

AF:

0.00471

Gnomad AMR exome

AF:

0.00881

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.000835

Gnomad SAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.0245

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0236

AC:

34542

AN:

1461186

Hom.:

490

Cov.:

AF XY:

0.0240

AC XY:

17410

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00347

Gnomad4 AMR exome

AF:

0.00946

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0264

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0156

AC:

2376

AN:

152184

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1102

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00457

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.0245

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0224

EpiControl

AF:

0.0234

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 26, 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

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.3

DANN

Benign

0.67

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