Variant 1-200848111-A-G 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_203459.4(CAMSAP2):c.1342A>G(p.Ile448Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,610,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000082 ( 1 hom. )

Consequence

CAMSAP2
NM_203459.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13265118).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP2	NM_203459.4 linkuse as main transcript	c.1342A>G	p.Ile448Val	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.1342A>G	p.Ile448Val	missense_variant	11/17	5	NM_203459.4	P3	Q08AD1-3
CAMSAP2	ENST00000236925.8 linkuse as main transcript	c.1375A>G	p.Ile459Val	missense_variant	12/18	1			Q08AD1-1
CAMSAP2	ENST00000413307.6 linkuse as main transcript	c.1294A>G	p.Ile432Val	missense_variant	11/17	1		A2	Q08AD1-2
CAMSAP2	ENST00000447701.2 linkuse as main transcript	c.395+819A>G		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248548

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1458206

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725504

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000452

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 26, 2023

The c.1342A>G (p.I448V) alteration is located in exon 11 (coding exon 11) of the CAMSAP2 gene. This alteration results from a A to G substitution at nucleotide position 1342, causing the isoleucine (I) at amino acid position 448 to be replaced by a valine (V). 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

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

.;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.046

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.0047

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.018

D;T;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.023

B;B;B

Vest4

0.31

MutPred

0.23

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

MVP

0.20

MPC

0.29

ClinPred

0.49

GERP RS

4.5

Varity_R

0.12

gMVP

0.27

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