2-127648346-C-T

Position:

• chr2-127648346-C-T

Variant summary

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

The ENST00000355119.9(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 ENST00000355119.9 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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LIMS2	NM_001161403.3	c.360-5274G>A		intron_variant		ENST00000355119.9	NP_001154875.1
GPR17	NM_001161417.2	c.-21+2102C>T		intron_variant		ENST00000486700.2	NP_001154889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9	c.360-5274G>A		intron_variant		1	NM_001161403.3	ENSP00000347240	P1
GPR17	ENST00000486700.2	c.-21+2102C>T		intron_variant		1	NM_001161417.2	ENSP00000508383	P1

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

Gnomad4 AMR exome AF: 0.0538

Gnomad4 ASJ exome AF: 0.0389

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0558

Gnomad4 OTH exome AF: 0.0695

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

Gnomad4 AMR AF: 0.0600

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0644 Hom.: 450

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

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;