6-17421641-C-A

Position:

• chr6-17421641-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20169699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAP2	NM_006366.3	c.86C>A	p.Pro29His	missense_variant	2/13	ENST00000229922.7
CAP2	NM_001363534.2	c.86C>A	p.Pro29His	missense_variant	2/12
CAP2	NM_001363533.2	c.86C>A	p.Pro29His	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAP2	ENST00000229922.7	c.86C>A	p.Pro29His	missense_variant	2/13	1	NM_006366.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

CAP2-associated dilated cardiomyopathy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

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;T;.;T;.;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.74	T;T;T;T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;.;.;.;.;N;N
MutationTaster	Benign	0.93	D;D;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N;.;.;N;N;D;N
REVEL	Benign	0.034
Sift	Benign	0.22	T;.;.;T;T;T;T
Sift4G	Benign	0.063	T;T;T;T;T;T;T
Polyphen		0.011	B;.;.;B;B;.;.
Vest4		0.26
MutPred		0.37		Loss of catalytic residue at P28 (P = 0.0191);Loss of catalytic residue at P28 (P = 0.0191);Loss of catalytic residue at P28 (P = 0.0191);Loss of catalytic residue at P28 (P = 0.0191);Loss of catalytic residue at P28 (P = 0.0191);Loss of catalytic residue at P28 (P = 0.0191);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-17421872;