Variant 1-200847220-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_203459.4(CAMSAP2):c.1120G>T(p.Ala374Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,608,092 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

CAMSAP2
NM_203459.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008588463).

BS2

High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP2	NM_203459.4 linkuse as main transcript	c.1120G>T	p.Ala374Ser	missense_variant	9/17	ENST00000358823.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP2	ENST00000358823.7 linkuse as main transcript	c.1120G>T	p.Ala374Ser	missense_variant	9/17	5	NM_203459.4	P3	Q08AD1-3
CAMSAP2	ENST00000236925.8 linkuse as main transcript	c.1153G>T	p.Ala385Ser	missense_variant	10/18	1			Q08AD1-1
CAMSAP2	ENST00000413307.6 linkuse as main transcript	c.1110-38G>T		intron_variant		1		A2	Q08AD1-2
CAMSAP2	ENST00000447701.2 linkuse as main transcript	c.325G>T	p.Ala109Ser	missense_variant, NMD_transcript_variant	4/6	4

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000117

AC:

AN:

248900

Hom.:

AF XY:

0.0000669

AC XY:

AN XY:

134590

show subpopulations

Gnomad AFR exome

AF:

0.00154

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:

0.0000265

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000687

AC:

100

AN:

1455878

Hom.:

Cov.:

AF XY:

0.0000649

AC XY:

AN XY:

724428

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000244

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.000407

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000804

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

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

Apr 07, 2022

The c.1120G>T (p.A374S) alteration is located in exon 9 (coding exon 9) of the CAMSAP2 gene. This alteration results from a G to T substitution at nucleotide position 1120, causing the alanine (A) at amino acid position 374 to be replaced by a serine (S). 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

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0078

.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

.;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.063

Sift

Benign

0.31

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.0070

B;B

Vest4

0.16

MVP

0.20

MPC

0.27

ClinPred

0.013

GERP RS

3.0

Varity_R

0.035

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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