NM_016366.3:c.659G>C

Variant names:

• chr11-67519143-C-G
• rs143180247
• NM_016366.3:c.659G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016366.3(CABP2):​c.659G>C​(p.Arg220Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CABP2 NM_016366.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49

Genes affected

CABP2 (HGNC:1385): (calcium binding protein 2) This gene belongs to a subfamily of calcium binding proteins that share similarity to calmodulin. Like calmodulin, these family members can likely stimulate calmodulin-dependent kinase II and the protein phosphatase calcineurin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP2	NM_016366.3	c.659G>C	p.Arg220Pro	missense_variant	Exon 7 of 7	ENST00000294288.5	NP_057450.2
CABP2	NM_001318496.2	c.677G>C	p.Arg226Pro	missense_variant	Exon 7 of 7		NP_001305425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP2	ENST00000294288.5	c.659G>C	p.Arg220Pro	missense_variant	Exon 7 of 7	1	NM_016366.3	ENSP00000294288.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	0.91	.;L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.6	D;D;.
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.0040	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.57
MutPred		0.51		.;Loss of solvent accessibility (P = 0.0364);.;
MVP		0.81
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.74
gMVP		0.68

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: rs143180247; hg19: chr11-67286614;