rs12456021

Positions:

• chr18-58546158-G-A
• chr18-58546158-G-C
• chr18-58546158-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPK2	NM_052947.4	c.1963-7934C>T		intron_variant		ENST00000361673.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPK2	ENST00000361673.4	c.1963-7934C>T		intron_variant		1	NM_052947.4	P1
ALPK2	ENST00000587399.1	n.400-1483C>T		intron_variant, non_coding_transcript_variant		2
ALPK2	ENST00000587842.1	n.212-940C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.185

Alfa AF: 0.185 Hom.: 5838

Bravo AF: 0.162

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs12456021; hg19: chr18-56213390;