NM_052947.4:c.*7T>C

Variant names:

• chr18-58481816-A-G
• rs3744867
• NM_052947.4:c.*7T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_052947.4(ALPK2):​c.*7T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,609,700 control chromosomes in the GnomAD database, including 145,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.42 (13907 hom., cov: 33)
  • Exomes 𝑓: 0.42 (131923 hom.)
• Consequence: ALPK2 NM_052947.4 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.40

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 18-58481816-A-G is Benign according to our data. Variant chr18-58481816-A-G is described in ClinVar as [Benign]. Clinvar id is 3059320.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-58481816-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK2	NM_052947.4	c.*7T>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000361673.4	NP_443179.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK2	ENST00000361673	c.*7T>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_052947.4	ENSP00000354991.3

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64372 AN: 151968 Hom.: 13898 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.433

GnomAD3 exomes AF: 0.394 AC: 99013 AN: 251056 Hom.: 20369 AF XY: 0.398 AC XY: 54018 AN XY: 135704

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.348

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.424

GnomAD4 exome AF: 0.422 AC: 615340 AN: 1457614 Hom.: 131923 Cov.: 30 AF XY: 0.421 AC XY: 305082 AN XY: 725422

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.424 AC: 64420 AN: 152086 Hom.: 13907 Cov.: 33 AF XY: 0.425 AC XY: 31617 AN XY: 74318

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.433

Alfa AF: 0.431 Hom.: 18410

Bravo AF: 0.410

Asia WGS AF: 0.294 AC: 1020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ALPK2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.010
DANN	Benign	0.39

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: rs3744867; hg19: chr18-56149048; COSMIC: COSV64493562; COSMIC: COSV64493562;