NM_006366.3:c.86C>A

Variant names:

• chr6-17421641-C-A
• rs2113531889
• NM_006366.3:c.86C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006366.3(CAP2):​c.86C>A​(p.Pro29His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAP2 NM_006366.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.906
• Publications: 0 publications found

Genes affected

CAP2 (HGNC:20039): (cyclase associated actin cytoskeleton regulatory protein 2) This gene was identified by its similarity to the gene for human adenylyl cyclase-associated protein. The function of the protein encoded by this gene is unknown. However, the protein appears to be able to interact with adenylyl cyclase-associated protein and actin. [provided by RefSeq, Jul 2008]

CAP2 Gene-Disease associations (from GenCC):

• cardiomyopathy, dilated, 2I

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=0.20169699).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006366.3. 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
	CAP2	NM_006366.3	MANE Select	c.86C>A	p.Pro29His	missense	Exon 2 of 13	NP_006357.1	P40123-1
	CAP2	NM_001363534.2		c.86C>A	p.Pro29His	missense	Exon 2 of 12	NP_001350463.1	E9PDI2
	CAP2	NM_001363533.2		c.86C>A	p.Pro29His	missense	Exon 2 of 10	NP_001350462.1	B7Z385

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAP2	ENST00000229922.7	TSL:1 MANE Select	c.86C>A	p.Pro29His	missense	Exon 2 of 13	ENSP00000229922.2	P40123-1
	CAP2	ENST00000479291.5	TSL:1	n.86C>A		non_coding_transcript_exon	Exon 2 of 12	ENSP00000420615.1	F8WDB9
	CAP2	ENST00000857692.1		c.86C>A	p.Pro29His	missense	Exon 2 of 14	ENSP00000527751.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	CAP2-associated dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.91
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.034
Sift	Benign	0.22	T
Sift4G	Benign	0.063	T
Polyphen		0.011	B
Vest4		0.26
MutPred		0.37		Loss of catalytic residue at P28 (P = 0.0191)
MVP		0.39
MPC		0.28
ClinPred		0.47	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.32
Mutation Taster		=95/5	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: rs2113531889; hg19: chr6-17421872;