rs6459541

Variant names:

• chr6-17405815-G-A
• rs6459541
• NM_006366.3:c.-2+12069G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-17405815-G-A
• chr6-17405815-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006366.3(CAP2):​c.-2+12069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,936 control chromosomes in the GnomAD database, including 11,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (11416 hom., cov: 32)
• Consequence: CAP2 NM_006366.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAP2	NM_006366.3	c.-2+12069G>A		intron_variant	Intron 1 of 12	ENST00000229922.7	NP_006357.1
CAP2	NM_001363534.2	c.-2+12069G>A		intron_variant	Intron 1 of 11		NP_001350463.1
CAP2	NM_001363533.2	c.-2+12069G>A		intron_variant	Intron 1 of 9		NP_001350462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAP2	ENST00000229922.7	c.-2+12069G>A		intron_variant	Intron 1 of 12	1	NM_006366.3	ENSP00000229922.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55185 AN: 151818 Hom.: 11383 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55259 AN: 151936 Hom.: 11416 Cov.: 32 AF XY: 0.360 AC XY: 26762 AN XY: 74248

African (AFR) AF: 0.574 AC: 23778 AN: 41424

American (AMR) AF: 0.287 AC: 4386 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 973 AN: 3470

East Asian (EAS) AF: 0.187 AC: 967 AN: 5158

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4814

European-Finnish (FIN) AF: 0.309 AC: 3263 AN: 10550

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19286 AN: 67952

Other (OTH) AF: 0.343 AC: 722 AN: 2108

Alfa AF: 0.323 Hom.: 1115

Bravo AF: 0.368

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs6459541; hg19: chr6-17406046;