dbSNP rs2243934: LIMS2:c.360-5274G>T (chr2-127648346-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001161403.3(LIMS2):c.360-5274G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LIMS2
NM_001161403.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.210

Publications

10 publications found

Variant links:

Genes affected

LIMS2 (HGNC:16084): (LIM zinc finger domain containing 2) This gene encodes a member of a small family of focal adhesion proteins which interacts with ILK (integrin-linked kinase), a protein which effects protein-protein interactions with the extraceullar matrix. The encoded protein has five LIM domains, each domain forming two zinc fingers, which permit interactions which regulate cell shape and migration. A pseudogene of this gene is located on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

LIMS2 links:

GPR17 (HGNC:4471): (G protein-coupled receptor 17) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of Rho protein signal transduction and positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to act upstream of or within negative regulation of inflammatory response to antigenic stimulus. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161403.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIMS2	NM_001161403.3	MANE Select	c.360-5274G>T	intron	N/A	NP_001154875.1	Q7Z4I7-1
GPR17	NM_001161417.2	MANE Select	c.-21+2102C>A	intron	N/A	NP_001154889.1	Q13304-2
GPR17	NM_001161415.2		c.-2+60C>A	intron	N/A	NP_001154887.1	Q13304-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.360-5274G>T	intron	N/A	ENSP00000347240.4	Q7Z4I7-1
GPR17	ENST00000486700.2	TSL:1 MANE Select	c.-21+2102C>A	intron	N/A	ENSP00000508383.1	Q13304-2
GPR17	ENST00000272644.7	TSL:1	c.-1-1665C>A	intron	N/A	ENSP00000272644.3	Q13304-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

146760

Hom.:

AF XY:

0.00

AC XY:

AN XY:

70186

African (AFR)

AF:

0.00

AC:

AN:

2738

American (AMR)

AF:

0.00

AC:

AN:

186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

902

East Asian (EAS)

AF:

0.00

AC:

AN:

592

South Asian (SAS)

AF:

0.00

AC:

AN:

2938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

134274

Other (OTH)

AF:

0.00

AC:

AN:

4802

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

630

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.3

(source)

DANN

Benign

0.89

PhyloP100

-0.21

PromoterAI

-0.020

Neutral

(source)

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

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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