Variant 1-200848117-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_203459.4(CAMSAP2):c.1348C>T(p.Arg450Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CAMSAP2
NM_203459.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

CAMSAP2 (HGNC:29188): (calmodulin regulated spectrin associated protein family member 2) Enables microtubule minus-end binding activity. Involved in several processes, including axon development; regulation of dendrite development; and regulation of organelle organization. Located in cytosol and microtubule end. Colocalizes with Golgi apparatus; centrosome; and microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

CAMSAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP2	NM_203459.4 linkuse as main transcript	c.1348C>T	p.Arg450Cys	missense_variant	11/17	ENST00000358823.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP2	ENST00000358823.7 linkuse as main transcript	c.1348C>T	p.Arg450Cys	missense_variant	11/17	5	NM_203459.4	P3	Q08AD1-3
CAMSAP2	ENST00000236925.8 linkuse as main transcript	c.1381C>T	p.Arg461Cys	missense_variant	12/18	1			Q08AD1-1
CAMSAP2	ENST00000413307.6 linkuse as main transcript	c.1300C>T	p.Arg434Cys	missense_variant	11/17	1		A2	Q08AD1-2
CAMSAP2	ENST00000447701.2 linkuse as main transcript	c.395+825C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458106

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

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

Sep 01, 2021

The c.1348C>T (p.R450C) alteration is located in exon 11 (coding exon 11) of the CAMSAP2 gene. This alteration results from a C to T substitution at nucleotide position 1348, causing the arginine (R) at amino acid position 450 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

0.40

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.43

.;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

.;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.79

MutPred

0.56

.;.;Loss of sheet (P = 0.0126);

MVP

0.67

MPC

0.61

ClinPred

0.99

GERP RS

3.5

Varity_R

0.79

gMVP

0.73

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