rs2300835

Variant names:

• chr14-32738316-C-A
• rs2300835
• NM_004274.5:c.3372+2434C>A

Variant summary

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

The NM_004274.5(AKAP6):​c.3372+2434C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,894 control chromosomes in the GnomAD database, including 2,041 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 0.16 (2041 hom., cov: 32)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 13 publications found

Genes affected

AKAP6 (HGNC:376): (A-kinase anchoring protein 6) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is highly expressed in various brain regions and cardiac and skeletal muscle. It is specifically localized to the sarcoplasmic reticulum and nuclear membrane, and is involved in anchoring PKA to the nuclear membrane or sarcoplasmic reticulum. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.3372+2434C>A		intron_variant	Intron 11 of 13	ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.3372+2434C>A		intron_variant	Intron 11 of 13	1	NM_004274.5	ENSP00000280979.4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24554 AN: 151776 Hom.: 2040 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.162 AC: 24563 AN: 151894 Hom.: 2041 Cov.: 32 AF XY: 0.159 AC XY: 11795 AN XY: 74214

African (AFR) AF: 0.152 AC: 6296 AN: 41454

American (AMR) AF: 0.169 AC: 2570 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3470

East Asian (EAS) AF: 0.0890 AC: 458 AN: 5148

South Asian (SAS) AF: 0.145 AC: 700 AN: 4814

European-Finnish (FIN) AF: 0.121 AC: 1277 AN: 10540

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11958 AN: 67918

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.172 Hom.: 10167

Bravo AF: 0.167

Asia WGS AF: 0.110 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.43
PhyloP100		1.2
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: rs2300835; hg19: chr14-33207522;