2-219598144-C-G

Variant names:

• chr2-219598144-C-G
• rs1697856261
• NM_052902.4:c.25C>G

Variant summary

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

The NM_052902.4(STK11IP):​c.25C>G​(p.Leu9Val) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK11IP NM_052902.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.654

Genes affected

STK11IP (HGNC:19184): (serine/threonine kinase 11 interacting protein) Enables protein kinase binding activity. Involved in protein localization. Located in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049821943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11IP	NM_052902.4	c.25C>G	p.Leu9Val	missense_variant	Exon 2 of 25	ENST00000456909.6	NP_443134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11IP	ENST00000456909.6	c.25C>G	p.Leu9Val	missense_variant	Exon 2 of 25	1	NM_052902.4	ENSP00000389383.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58C>G (p.L20V) alteration is located in exon 2 (coding exon 2) of the STK11IP gene. This alteration results from a C to G substitution at nucleotide position 58, causing the leucine (L) at amino acid position 20 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.8
DANN	Benign	0.85
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.012
Sift	Benign	0.34	T
Sift4G	Benign	0.24	T
Vest4		0.20
MVP		0.014
ClinPred		0.18	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1697856261; hg19: chr2-220462866;