1-200739897-C-T

Position:

• chr1-200739897-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_203459.4(CAMSAP2):​c.70C>T​(p.His24Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.50

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CAMSAP2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP2	NM_203459.4	c.70C>T	p.His24Tyr	missense_variant	1/17	ENST00000358823.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP2	ENST00000358823.7	c.70C>T	p.His24Tyr	missense_variant	1/17	5	NM_203459.4	P3
CAMSAP2	ENST00000236925.8	c.70C>T	p.His24Tyr	missense_variant	1/18	1
CAMSAP2	ENST00000413307.6	c.70C>T	p.His24Tyr	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

Oct 18, 2021

The c.70C>T (p.H24Y) alteration is located in exon 1 (coding exon 1) of the CAMSAP2 gene. This alteration results from a C to T substitution at nucleotide position 70, causing the histidine (H) at amino acid position 24 to be replaced by a tyrosine (Y). 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	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.53
MutPred		0.27		Gain of methylation at K20 (P = 0.1314);Gain of methylation at K20 (P = 0.1314);Gain of methylation at K20 (P = 0.1314);
MVP		0.093
MPC		1.0
ClinPred		0.97	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-200709025; COSMIC: COSV105100526;