2-127648346-C-T

Variant names:

• chr2-127648346-C-T
• rs2243934
• NM_001161403.3:c.360-5274G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161403.3(LIMS2):​c.360-5274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 298,850 control chromosomes in the GnomAD database, including 693 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 0.069 (395 hom., cov: 31)
  • Exomes 𝑓: 0.058 (298 hom.)
• Consequence: LIMS2 NM_001161403.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 10 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10463 AN: 152132 Hom.: 392 Cov.: 31

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0693

GnomAD4 exome AF: 0.0575 AC: 8434 AN: 146600 Hom.: 298 AF XY: 0.0574 AC XY: 4023 AN XY: 70090

African (AFR) AF: 0.0702 AC: 192 AN: 2734

American (AMR) AF: 0.0538 AC: 10 AN: 186

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 35 AN: 900

East Asian (EAS) AF: 0.100 AC: 59 AN: 590

South Asian (SAS) AF: 0.105 AC: 308 AN: 2934

European-Finnish (FIN) AF: 0.0250 AC: 1 AN: 40

Middle Eastern (MID) AF: 0.0490 AC: 14 AN: 286

European-Non Finnish (NFE) AF: 0.0558 AC: 7482 AN: 134136

Other (OTH) AF: 0.0695 AC: 333 AN: 4794

GnomAD4 genome AF: 0.0689 AC: 10494 AN: 152250 Hom.: 395 Cov.: 31 AF XY: 0.0679 AC XY: 5056 AN XY: 74432

African (AFR) AF: 0.0784 AC: 3257 AN: 41528

American (AMR) AF: 0.0600 AC: 918 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.114 AC: 588 AN: 5180

South Asian (SAS) AF: 0.113 AC: 545 AN: 4822

European-Finnish (FIN) AF: 0.0254 AC: 270 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0661 AC: 4497 AN: 68006

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0656 Hom.: 630

Bravo AF: 0.0696

Asia WGS AF: 0.120 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		-0.21
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2243934; hg19: chr2-128405921;