chr2-127648346-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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMS2	NM_001161403.3	c.360-5274G>A		intron_variant	Intron 4 of 9	ENST00000355119.9	NP_001154875.1
GPR17	NM_001161417.2	c.-21+2102C>T		intron_variant	Intron 1 of 1	ENST00000486700.2	NP_001154889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9	c.360-5274G>A		intron_variant	Intron 4 of 9	1	NM_001161403.3	ENSP00000347240.4
GPR17	ENST00000486700.2	c.-21+2102C>T		intron_variant	Intron 1 of 1	1	NM_001161417.2	ENSP00000508383.1

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

Gnomad4 AFR exome AF: 0.0702 AC: 192 AN: 2734

Gnomad4 AMR exome AF: 0.0538 AC: 10 AN: 186

Gnomad4 ASJ exome AF: 0.0389 AC: 35 AN: 900

Gnomad4 EAS exome AF: 0.100 AC: 59 AN: 590

Gnomad4 SAS exome AF: 0.105 AC: 308 AN: 2934

Gnomad4 FIN exome AF: 0.0250 AC: 1 AN: 40

Gnomad4 NFE exome AF: 0.0558 AC: 7482 AN: 134136

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0784 AC: 0.078429 AN: 0.078429

Gnomad4 AMR AF: 0.0600 AC: 0.0599922 AN: 0.0599922

Gnomad4 ASJ AF: 0.0501 AC: 0.0501441 AN: 0.0501441

Gnomad4 EAS AF: 0.114 AC: 0.113514 AN: 0.113514

Gnomad4 SAS AF: 0.113 AC: 0.113024 AN: 0.113024

Gnomad4 FIN AF: 0.0254 AC: 0.0254189 AN: 0.0254189

Gnomad4 NFE AF: 0.0661 AC: 0.0661265 AN: 0.0661265

Gnomad4 OTH AF: 0.0724 AC: 0.0723746 AN: 0.0723746

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.88
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

Publications

LitVar

Other links and lift over

dbSNP: rs2243934; hg19: chr2-128405921;