rs7926485

Positions:

• chr11-111665946-G-A
• chr11-111665946-G-C
• chr11-111665946-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015191.3(SIK2):​c.317-22055G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,116 control chromosomes in the GnomAD database, including 31,521 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (31521 hom., cov: 33)
• Consequence: SIK2 NM_015191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK2	NM_015191.3	c.317-22055G>A		intron_variant		ENST00000304987.4	NP_056006.1
SIK2	XM_017017417.2	c.107-22055G>A		intron_variant			XP_016872906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK2	ENST00000304987.4	c.317-22055G>A		intron_variant		1	NM_015191.3	ENSP00000305976	P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93196 AN: 151998 Hom.: 31497 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.613 AC: 93253 AN: 152116 Hom.: 31521 Cov.: 33 AF XY: 0.620 AC XY: 46083 AN XY: 74384

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.606

Alfa AF: 0.682 Hom.: 34664

Bravo AF: 0.600

Asia WGS AF: 0.819 AC: 2848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs7926485; hg19: chr11-111536670;