NM_203459.4:c.638G>A

Variant names:

• chr1-200815637-G-A
• rs374737109
• NM_203459.4:c.638G>A

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.638G>A​(p.Gly213Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,610 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. G213V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CAMSAP2 NM_203459.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 1 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=0.16164923).

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.638G>A	p.Gly213Asp	missense	Exon 4 of 17	NP_982284.1	Q08AD1-3
	CAMSAP2	NM_001297707.3		c.638G>A	p.Gly213Asp	missense	Exon 4 of 18	NP_001284636.1	Q08AD1-1
	CAMSAP2	NM_001389638.1		c.638G>A	p.Gly213Asp	missense	Exon 4 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.638G>A	p.Gly213Asp	missense	Exon 4 of 17	ENSP00000351684.2	Q08AD1-3
	CAMSAP2	ENST00000236925.9	TSL:1	c.638G>A	p.Gly213Asp	missense	Exon 4 of 18	ENSP00000236925.4	Q08AD1-1
	CAMSAP2	ENST00000413307.6	TSL:1	c.638G>A	p.Gly213Asp	missense	Exon 4 of 17	ENSP00000416800.2	Q08AD1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399610 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 695138

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30912

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24560

East Asian (EAS) AF: 0.00 AC: 0 AN: 37632

South Asian (SAS) AF: 0.00 AC: 0 AN: 73332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1082168

Other (OTH) AF: 0.00 AC: 0 AN: 57730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.092
Sift	Benign	0.27	T
Sift4G	Benign	0.46	T
Polyphen		0.96	D
Vest4		0.54
MutPred		0.19		Loss of MoRF binding (P = 0.0622)
MVP		0.17
MPC		0.61
ClinPred		0.57	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.26
Mutation Taster		=90/10	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: rs374737109; hg19: chr1-200784765;