Genetic Variant NM_052947.4:c.6507A>T (chr18-58481829-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052947.4(ALPK2):c.6507A>T(p.Lys2169Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ALPK2
NM_052947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.741

Publications

0 publications found

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:

ENSG00000296058 (HGNC:):

ENSG00000296058 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25214604).

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.6507A>T	p.Lys2169Asn	missense	Exon 13 of 13	NP_443179.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALPK2	ENST00000361673.4	TSL:1 MANE Select	c.6507A>T	p.Lys2169Asn	missense	Exon 13 of 13	ENSP00000354991.3	Q86TB3
ALPK2	ENST00000941324.1		c.6471A>T	p.Lys2157Asn	missense	Exon 12 of 12	ENSP00000611383.1
ALPK2	ENST00000857519.1		c.3414A>T	p.Lys1138Asn	missense	Exon 13 of 13	ENSP00000527578.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251242

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461530

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33398

American (AMR)

AF:

0.0000448

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111858

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

0.017

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.40

M_CAP

Benign

0.032

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.1

PhyloP100

0.74

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.13

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.060

MutPred

0.20

Loss of methylation at K2169 (P = 0.004)

MVP

0.75

MPC

0.18

ClinPred

0.91

GERP RS

0.61

Varity_R

0.33

gMVP

0.19

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over