rs2268952

Variant names:

• chr14-32828349-C-T
• rs2268952
• NM_004274.5:c.*43-1499C>T

Variant summary

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

The NM_004274.5(AKAP6):​c.*43-1499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,186 control chromosomes in the GnomAD database, including 554 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 0.078 (554 hom., cov: 32)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 1 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]

ENSG00000302430 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.*43-1499C>T		intron_variant	Intron 13 of 13	ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.*43-1499C>T		intron_variant	Intron 13 of 13	1	NM_004274.5	ENSP00000280979.4
AKAP6	ENST00000557272.1	c.3589-1499C>T		intron_variant	Intron 12 of 12	5		ENSP00000451247.1
ENSG00000302430	ENST00000786608.1	n.279-6888G>A		intron_variant	Intron 2 of 2
ENSG00000302430	ENST00000786609.1	n.215-6888G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11884 AN: 152068 Hom.: 547 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0782 AC: 11905 AN: 152186 Hom.: 554 Cov.: 32 AF XY: 0.0808 AC XY: 6012 AN XY: 74390

African (AFR) AF: 0.0955 AC: 3961 AN: 41494

American (AMR) AF: 0.0571 AC: 874 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 283 AN: 3472

East Asian (EAS) AF: 0.171 AC: 882 AN: 5172

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4820

European-Finnish (FIN) AF: 0.0503 AC: 533 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4114 AN: 68018

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0739 Hom.: 268

Bravo AF: 0.0752

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.76
DANN	Benign	0.62
PhyloP100		-1.5
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: rs2268952; hg19: chr14-33297555;