1-200848630-G-A

Position:

• chr1-200848630-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_203459.4(CAMSAP2):​c.1861G>A​(p.Glu621Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 6.06

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CAMSAP2
• BP4: Computational evidence support a benign effect (MetaRNN=0.1301873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP2	NM_203459.4	c.1861G>A	p.Glu621Lys	missense_variant	11/17	ENST00000358823.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP2	ENST00000358823.7	c.1861G>A	p.Glu621Lys	missense_variant	11/17	5	NM_203459.4	P3
CAMSAP2	ENST00000236925.8	c.1894G>A	p.Glu632Lys	missense_variant	12/18	1
CAMSAP2	ENST00000413307.6	c.1813G>A	p.Glu605Lys	missense_variant	11/17	1		A2
CAMSAP2	ENST00000447701.2	c.395+1338G>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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

Jan 31, 2023

The c.1861G>A (p.E621K) alteration is located in exon 11 (coding exon 11) of the CAMSAP2 gene. This alteration results from a G to A substitution at nucleotide position 1861, causing the glutamic acid (E) at amino acid position 621 to be replaced by a lysine (K). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Benign	0.97
Eigen	Benign	0.070
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.56	N;N;N
REVEL	Benign	0.048
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.66	T;T;T
Polyphen		0.59	P;B;B
Vest4		0.29
MutPred		0.27		.;.;Gain of ubiquitination at E632 (P = 6e-04);
MVP		0.22
MPC		0.70
ClinPred		0.61	D
GERP RS		4.8
Varity_R		0.076
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs1667526173; hg19: chr1-200817758;