dbSNP rs867925729: CLASP2:p.Asp1442Asp (chr3-33501760-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001365631.1(CLASP2):c.4326T>C(p.Asp1442Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,610,692 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 1 hom. )

Consequence

CLASP2
NM_001365631.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.84

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 3-33501760-A-G is Benign according to our data. Variant chr3-33501760-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3047500.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BS2

High AC in GnomAdExome4 at 26 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLASP2	NM_001365631.1	MANE Select	c.4326T>C	p.Asp1442Asp	synonymous	Exon 38 of 39	NP_001352560.1	A0A804HJG7
CLASP2	NM_001365628.1		c.4413T>C	p.Asp1471Asp	synonymous	Exon 39 of 40	NP_001352557.1
CLASP2	NM_001365629.1		c.4410T>C	p.Asp1470Asp	synonymous	Exon 39 of 40	NP_001352558.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLASP2	ENST00000682230.1	MANE Select	c.4326T>C	p.Asp1442Asp	synonymous	Exon 38 of 39	ENSP00000507498.1	A0A804HJG7
CLASP2	ENST00000468888.6	TSL:5	c.4350T>C	p.Asp1450Asp	synonymous	Exon 38 of 39	ENSP00000419974.2	E7EW49
CLASP2	ENST00000399362.8	TSL:5	c.4347T>C	p.Asp1449Asp	synonymous	Exon 38 of 39	ENSP00000382297.4	E7ERI8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

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:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1458396

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725720

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109074

Other (OTH)

AF:

0.0000332

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CLASP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.1

(source)

DANN

Benign

0.55

PhyloP100

1.8

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over