chr1-200832721-A-G

Variant names:

• chr1-200832721-A-G
• rs375906378
• NM_203459.4:c.803A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203459.4(CAMSAP2):​c.803A>G​(p.Glu268Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E268A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAMSAP2 NM_203459.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36233187).

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.803A>G	p.Glu268Gly	missense	Exon 6 of 17	NP_982284.1	Q08AD1-3
	CAMSAP2	NM_001297707.3		c.836A>G	p.Glu279Gly	missense	Exon 7 of 18	NP_001284636.1	Q08AD1-1
	CAMSAP2	NM_001389638.1		c.836A>G	p.Glu279Gly	missense	Exon 7 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.803A>G	p.Glu268Gly	missense	Exon 6 of 17	ENSP00000351684.2	Q08AD1-3
	CAMSAP2	ENST00000236925.9	TSL:1	c.836A>G	p.Glu279Gly	missense	Exon 7 of 18	ENSP00000236925.4	Q08AD1-1
	CAMSAP2	ENST00000413307.6	TSL:1	c.803A>G	p.Glu268Gly	missense	Exon 6 of 17	ENSP00000416800.2	Q08AD1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000420 AC: 1 AN: 238266 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000321

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: 6.91e-7 AC: 1 AN: 1446768 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 718890

African (AFR) AF: 0.00 AC: 0 AN: 32582

American (AMR) AF: 0.0000242 AC: 1 AN: 41264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25614

East Asian (EAS) AF: 0.00 AC: 0 AN: 39398

South Asian (SAS) AF: 0.00 AC: 0 AN: 82062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107216

Other (OTH) AF: 0.00 AC: 0 AN: 59760

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.0044	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.97	D
Vest4		0.32
MutPred		0.37		Gain of catalytic residue at M281 (P = 0.0349)
MVP		0.24
MPC		0.99
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.68
gMVP		0.64
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs375906378; hg19: chr1-200801849;