dbSNP rs996558411: ALPK2:p.Gly2166Asp (chr18-58481839-C-T) – 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.6497G>A(p.Gly2166Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G2166G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALPK2
NM_052947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.318

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=0.09602186).

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.6497G>A	p.Gly2166Asp	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.6497G>A	p.Gly2166Asp	missense	Exon 13 of 13	ENSP00000354991.3	Q86TB3
ALPK2	ENST00000941324.1		c.6461G>A	p.Gly2154Asp	missense	Exon 12 of 12	ENSP00000611383.1
ALPK2	ENST00000857519.1		c.3404G>A	p.Gly1135Asp	missense	Exon 13 of 13	ENSP00000527578.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

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:

1111958

Other (OTH)

AF:

0.00

AC:

AN:

60394

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.034

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.44

M_CAP

Benign

0.027

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.32

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.050

Sift

Uncertain

0.0050

Sift4G

Benign

0.29

Polyphen

0.56

Vest4

0.16

MutPred

0.16

Gain of ubiquitination at K2168 (P = 0.0329)

MVP

0.32

MPC

0.14

ClinPred

0.22

GERP RS

2.2

Varity_R

0.19

gMVP

0.19

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