18-58481816-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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]

ENSG00000296058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 3059320.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK2	NM_052947.4	MANE Select	c.*7T>C		3_prime_UTR	Exon 13 of 13	NP_443179.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK2	ENST00000361673.4	TSL:1 MANE Select	c.*7T>C		3_prime_UTR	Exon 13 of 13	ENSP00000354991.3	Q86TB3
	ALPK2	ENST00000941324.1		c.*7T>C		3_prime_UTR	Exon 12 of 12	ENSP00000611383.1
	ALPK2	ENST00000857519.1		c.*7T>C		3_prime_UTR	Exon 13 of 13	ENSP00000527578.1

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

GnomAD2 exomes AF: 0.394 AC: 99013 AN: 251056 AF XY: 0.398

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 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

African (AFR) AF: 0.434 AC: 14478 AN: 33324

American (AMR) AF: 0.301 AC: 13419 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10210 AN: 26106

East Asian (EAS) AF: 0.281 AC: 11137 AN: 39674

South Asian (SAS) AF: 0.349 AC: 30089 AN: 86146

European-Finnish (FIN) AF: 0.522 AC: 27871 AN: 53404

Middle Eastern (MID) AF: 0.484 AC: 2784 AN: 5758

European-Non Finnish (NFE) AF: 0.433 AC: 479925 AN: 1108328

Other (OTH) AF: 0.422 AC: 25427 AN: 60254

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

African (AFR) AF: 0.428 AC: 17753 AN: 41490

American (AMR) AF: 0.373 AC: 5694 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1134 AN: 5178

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4816

European-Finnish (FIN) AF: 0.536 AC: 5660 AN: 10564

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29866 AN: 67978

Other (OTH) AF: 0.433 AC: 915 AN: 2114

Alfa AF: 0.430 Hom.: 22642

Bravo AF: 0.410

Asia WGS AF: 0.294 AC: 1020 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ALPK2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.010
DANN	Benign	0.39
PhyloP100		-1.4
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: rs3744867; hg19: chr18-56149048; COSMIC: COSV64493562; COSMIC: COSV64493562;