1-200739859-G-A

Variant names:

• chr1-200739859-G-A
• rs763707243
• NM_203459.4:c.32G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_203459.4(CAMSAP2):​c.32G>A​(p.Arg11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CAMSAP2 NM_203459.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.058423907).
• BS2: High AC in GnomAdExome4 at 24 AD gene.

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.32G>A	p.Arg11Lys	missense	Exon 1 of 17	NP_982284.1	Q08AD1-3
	CAMSAP2	NM_001297707.3		c.32G>A	p.Arg11Lys	missense	Exon 1 of 18	NP_001284636.1	Q08AD1-1
	CAMSAP2	NM_001389638.1		c.32G>A	p.Arg11Lys	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.32G>A	p.Arg11Lys	missense	Exon 1 of 17	ENSP00000351684.2	Q08AD1-3
	CAMSAP2	ENST00000236925.9	TSL:1	c.32G>A	p.Arg11Lys	missense	Exon 1 of 18	ENSP00000236925.4	Q08AD1-1
	CAMSAP2	ENST00000413307.6	TSL:1	c.32G>A	p.Arg11Lys	missense	Exon 1 of 17	ENSP00000416800.2	Q08AD1-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251380 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15 AN XY: 727232

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111994

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.085
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		2.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.060
Sift	Benign	0.19	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.36		Gain of ubiquitination at R11 (P = 0.0219)
MVP		0.082
MPC		0.30
ClinPred		0.069	T
GERP RS		2.6
PromoterAI		0.072	Neutral
Varity_R		0.11
gMVP		0.33
Mutation Taster		=96/4	polymorphism

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

dbSNP: rs763707243; hg19: chr1-200708987;