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. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R220Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CABP2 NM_016366.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49
• Publications: 1 publications found

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]

CABP2 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 93

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016366.3. 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
	CABP2	NM_016366.3	MANE Select	c.659G>C	p.Arg220Pro	missense	Exon 7 of 7	NP_057450.2	Q9NPB3-1
	CABP2	NM_001318496.2		c.677G>C	p.Arg226Pro	missense	Exon 7 of 7	NP_001305425.1	F1T0K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP2	ENST00000294288.5	TSL:1 MANE Select	c.659G>C	p.Arg220Pro	missense	Exon 7 of 7	ENSP00000294288.4	Q9NPB3-1
	CABP2	ENST00000545205.2	TSL:1	n.*444G>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000446180.1	F5H458
	CABP2	ENST00000545205.2	TSL:1	n.*444G>C		3_prime_UTR	Exon 7 of 7	ENSP00000446180.1	F5H458

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	0.91	L
PhyloP100		7.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	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
Mutation Taster		=74/26	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: rs143180247; hg19: chr11-67286614;