chr11-111602603-C-G

Variant names:

• chr11-111602603-C-G
• rs1941598239
• NM_015191.3:c.40C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_015191.3(SIK2):​c.40C>G​(p.Pro14Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,380,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SIK2 NM_015191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

Genes affected

SIK2 (HGNC:21680): (salt inducible kinase 2) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in intracellular signal transduction and protein autophosphorylation. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309590 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37703425).
• BS2: High AC in GnomAdExome4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015191.3. 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
	SIK2	NM_015191.3	MANE Select	c.40C>G	p.Pro14Ala	missense	Exon 1 of 15	NP_056006.1	Q9H0K1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIK2	ENST00000304987.4	TSL:1 MANE Select	c.40C>G	p.Pro14Ala	missense	Exon 1 of 15	ENSP00000305976.3	Q9H0K1
	SIK2	ENST00000876570.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 16	ENSP00000546629.1
	SIK2	ENST00000940048.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 15	ENSP00000610107.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000174 AC: 24 AN: 1380760 Hom.: 0 Cov.: 32 AF XY: 0.0000132 AC XY: 9 AN XY: 681404

African (AFR) AF: 0.00 AC: 0 AN: 28756

American (AMR) AF: 0.00 AC: 0 AN: 35088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24380

East Asian (EAS) AF: 0.00 AC: 0 AN: 32092

South Asian (SAS) AF: 0.00 AC: 0 AN: 77748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 0.0000215 AC: 23 AN: 1071648

Other (OTH) AF: 0.0000175 AC: 1 AN: 57228

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000625 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0095	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.82	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.44
Sift	Benign	0.072	T
Sift4G	Benign	0.12	T
Polyphen		0.64	P
Vest4		0.26
MutPred		0.39		Gain of MoRF binding (P = 0.0334)
MVP		0.19
MPC		2.2
ClinPred		1.0	D
GERP RS		4.3
PromoterAI		-0.11	Neutral
Varity_R		0.56
gMVP		0.37
Mutation Taster		=65/35	polymorphism

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: rs1941598239; hg19: chr11-111473327;