1-200739936-G-T

Position:

• chr1-200739936-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203459.4(CAMSAP2):​c.109G>T​(p.Ala37Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CAMSAP2 NM_203459.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1685878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP2	NM_203459.4	c.109G>T	p.Ala37Ser	missense_variant	1/17	ENST00000358823.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP2	ENST00000358823.7	c.109G>T	p.Ala37Ser	missense_variant	1/17	5	NM_203459.4	P3
CAMSAP2	ENST00000236925.8	c.109G>T	p.Ala37Ser	missense_variant	1/18	1
CAMSAP2	ENST00000413307.6	c.109G>T	p.Ala37Ser	missense_variant	1/17	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.109G>T (p.A37S) alteration is located in exon 1 (coding exon 1) of the CAMSAP2 gene. This alteration results from a G to T substitution at nucleotide position 109, causing the alanine (A) at amino acid position 37 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	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.022	.;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.83	T;D;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.040	N;N;N
REVEL	Benign	0.071
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.96	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.33
MutPred		0.42		Loss of ubiquitination at K42 (P = 0.1166);Loss of ubiquitination at K42 (P = 0.1166);Loss of ubiquitination at K42 (P = 0.1166);
MVP		0.093
MPC		0.28
ClinPred		0.63	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-200709064;