1-200807397-G-A

Variant names:

• chr1-200807397-G-A
• rs1300846903
• NM_203459.4:c.421G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_203459.4(CAMSAP2):​c.421G>A​(p.Asp141Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,398,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CAMSAP2 NM_203459.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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 Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917
• BS2: High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP2	NM_203459.4	c.421G>A	p.Asp141Asn	missense_variant	Exon 3 of 17	ENST00000358823.7	NP_982284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMSAP2	ENST00000358823.7	c.421G>A	p.Asp141Asn	missense_variant	Exon 3 of 17	5	NM_203459.4	ENSP00000351684.2
CAMSAP2	ENST00000236925.8	c.421G>A	p.Asp141Asn	missense_variant	Exon 3 of 18	1		ENSP00000236925.4
CAMSAP2	ENST00000413307.6	c.421G>A	p.Asp141Asn	missense_variant	Exon 3 of 17	1		ENSP00000416800.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000193 AC: 27 AN: 1398360 Hom.: 0 Cov.: 31 AF XY: 0.0000259 AC XY: 18 AN XY: 693738

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000242

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.421G>A (p.D141N) alteration is located in exon 3 (coding exon 3) of the CAMSAP2 gene. This alteration results from a G to A substitution at nucleotide position 421, causing the aspartic acid (D) at amino acid position 141 to be replaced by an asparagine (N). 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	0.41
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	.;.;D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.91
MutPred		0.76		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP		0.57
MPC		0.92
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.79
gMVP		0.78

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: rs1300846903; hg19: chr1-200776525;