NM_006366.3:c.703C>A

Variant names:

• chr6-17539335-C-A
• rs766800946
• NM_006366.3:c.703C>A

Variant summary

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

The NM_006366.3(CAP2):​c.703C>A​(p.Pro235Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P235A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CAP2 NM_006366.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04
• 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.

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.703C>A	p.Pro235Thr	missense	Exon 8 of 13	NP_006357.1	P40123-1
	CAP2	NM_001363534.2		c.625C>A	p.Pro209Thr	missense	Exon 7 of 12	NP_001350463.1	E9PDI2
	CAP2	NM_001363533.2		c.367C>A	p.Pro123Thr	missense	Exon 5 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.703C>A	p.Pro235Thr	missense	Exon 8 of 13	ENSP00000229922.2	P40123-1
	CAP2	ENST00000479291.5	TSL:1	n.*144C>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000420615.1	F8WDB9
	CAP2	ENST00000479291.5	TSL:1	n.*144C>A		3_prime_UTR	Exon 8 of 12	ENSP00000420615.1	F8WDB9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.24	D
PhyloP100		7.0
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.40
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs766800946; hg19: chr6-17539566;