chr1-200807382-C-T

Variant names:

• chr1-200807382-C-T
• NM_203459.4:c.406C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_203459.4(CAMSAP2):​c.406C>T​(p.His136Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.57
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203459.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP2	NM_203459.4	MANE Select	c.406C>T	p.His136Tyr	missense	Exon 3 of 17	NP_982284.1	Q08AD1-3
	CAMSAP2	NM_001297707.3		c.406C>T	p.His136Tyr	missense	Exon 3 of 18	NP_001284636.1	Q08AD1-1
	CAMSAP2	NM_001389638.1		c.406C>T	p.His136Tyr	missense	Exon 3 of 18	NP_001376567.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP2	ENST00000358823.7	TSL:5 MANE Select	c.406C>T	p.His136Tyr	missense	Exon 3 of 17	ENSP00000351684.2	Q08AD1-3
	CAMSAP2	ENST00000236925.9	TSL:1	c.406C>T	p.His136Tyr	missense	Exon 3 of 18	ENSP00000236925.4	Q08AD1-1
	CAMSAP2	ENST00000413307.6	TSL:1	c.406C>T	p.His136Tyr	missense	Exon 3 of 17	ENSP00000416800.2	Q08AD1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.28	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.54		Loss of disorder (P = 0.0493)
MVP		0.69
MPC		1.1
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.89
gMVP		0.89
Mutation Taster		=45/55	disease causing

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

Other links and lift over

hg19: chr1-200776510;