18-58546158-G-A

Variant names:

• chr18-58546158-G-A
• rs12456021
• NM_052947.4:c.1963-7934C>T

Variant summary

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

The NM_052947.4(ALPK2):​c.1963-7934C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,114 control chromosomes in the GnomAD database, including 2,423 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 (2423 hom., cov: 32)
• Consequence: ALPK2 NM_052947.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 23 publications found

Genes affected

ALPK2 (HGNC:20565): (alpha kinase 2) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Involved in several processes, including epicardium morphogenesis; heart development; and negative regulation of Wnt signaling pathway involved in heart development. Acts upstream of or within regulation of gene expression. Colocalizes with basolateral plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK2	NM_052947.4	MANE Select	c.1963-7934C>T		intron	N/A	NP_443179.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK2	ENST00000361673.4	TSL:1 MANE Select	c.1963-7934C>T		intron	N/A	ENSP00000354991.3
	ALPK2	ENST00000587399.1	TSL:2	n.400-1483C>T		intron	N/A
	ALPK2	ENST00000587842.1	TSL:4	n.212-940C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24874 AN: 151996 Hom.: 2417 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.164 AC: 24883 AN: 152114 Hom.: 2423 Cov.: 32 AF XY: 0.167 AC XY: 12428 AN XY: 74342

African (AFR) AF: 0.0553 AC: 2296 AN: 41514

American (AMR) AF: 0.208 AC: 3173 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1664 AN: 5176

South Asian (SAS) AF: 0.251 AC: 1207 AN: 4808

European-Finnish (FIN) AF: 0.217 AC: 2289 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12759 AN: 67982

Other (OTH) AF: 0.185 AC: 390 AN: 2112

Alfa AF: 0.181 Hom.: 9531

Bravo AF: 0.162

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		0.78
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: rs12456021; hg19: chr18-56213390;