Variant chr18-58481816-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000361673.4(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
ENST00000361673.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.40

Variant links:

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]

ALPK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
ALPK2	NM_052947.4 linkuse as main transcript	c.*7T>C		3_prime_UTR_variant	13/13	ENST00000361673.4	NP_443179.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK2	ENST00000361673.4 linkuse as main transcript	c.*7T>C		3_prime_UTR_variant	13/13	1	NM_052947.4	ENSP00000354991	P1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64372

AN:

151968

Hom.:

13898

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.421

AC XY:

305082

AN XY:

725422

show subpopulations

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.:

AF XY:

0.425

AC XY:

31617

AN XY:

74318

show subpopulations

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

LINK: link

Submissions by phenotype

ALPK2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over