18-58481852-G-A

Position:

• chr18-58481852-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000361673.4(ALPK2):​c.6484C>T​(p.Pro2162Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P2162P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALPK2 ENST00000361673.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029988319).
• BP6: Variant 18-58481852-G-A is Benign according to our data. Variant chr18-58481852-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2449219.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK2	NM_052947.4	c.6484C>T	p.Pro2162Ser	missense_variant	13/13	ENST00000361673.4	NP_443179.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK2	ENST00000361673.4	c.6484C>T	p.Pro2162Ser	missense_variant	13/13	1	NM_052947.4	ENSP00000354991	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0010
DANN	Benign	0.55
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Benign	0.99	T
Sift4G	Benign	0.90	T
Polyphen		0.0020	B
Vest4		0.031
MutPred		0.16		Gain of phosphorylation at P2162 (P = 0.0215);
MVP		0.061
MPC		0.096
ClinPred		0.085	T
GERP RS		-12
Varity_R		0.024
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-56149084;