1-200739888-C-T

Variant names:

• chr1-200739888-C-T
• rs756562159
• NM_203459.4:c.61C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203459.4(CAMSAP2):​c.61C>T​(p.Pro21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAMSAP2 NM_203459.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087322414).

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.61C>T	p.Pro21Ser	missense	Exon 1 of 17	NP_982284.1	Q08AD1-3
	CAMSAP2	NM_001297707.3		c.61C>T	p.Pro21Ser	missense	Exon 1 of 18	NP_001284636.1	Q08AD1-1
	CAMSAP2	NM_001389638.1		c.61C>T	p.Pro21Ser	missense	Exon 1 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.61C>T	p.Pro21Ser	missense	Exon 1 of 17	ENSP00000351684.2	Q08AD1-3
	CAMSAP2	ENST00000236925.9	TSL:1	c.61C>T	p.Pro21Ser	missense	Exon 1 of 18	ENSP00000236925.4	Q08AD1-1
	CAMSAP2	ENST00000413307.6	TSL:1	c.61C>T	p.Pro21Ser	missense	Exon 1 of 17	ENSP00000416800.2	Q08AD1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251464 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.10	N
PhyloP100		3.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.076
Sift	Benign	0.33	T
Sift4G	Benign	0.34	T
Polyphen		0.013	B
Vest4		0.31
MutPred		0.46		Loss of catalytic residue at P21 (P = 0.0418)
MVP		0.10
MPC		0.30
ClinPred		0.81	D
GERP RS		3.5
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.29
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs756562159; hg19: chr1-200709016; COSMIC: COSV52673736;