2-127654879-G-A

Variant names:

• chr2-127654879-G-A
• rs35765118
• NM_001161403.3:c.189C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001161403.3(LIMS2):​c.189C>T​(p.Tyr63Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,614,018 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (54 hom., cov: 33)
  • Exomes 𝑓: 0.016 (221 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.82
• Publications: 5 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.033).
• BP6: Variant 2-127654879-G-A is Benign according to our data. Variant chr2-127654879-G-A is described in ClinVar as Benign. ClinVar VariationId is 260984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0215 (3280/152344) while in subpopulation AFR AF = 0.0425 (1766/41572). AF 95% confidence interval is 0.0408. There are 54 homozygotes in GnomAd4. There are 1536 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 54 AR,Unknown gene

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.189C>T	p.Tyr63Tyr	synonymous	Exon 3 of 10	NP_001154875.1	Q7Z4I7-1
	LIMS2	NM_017980.5		c.261C>T	p.Tyr87Tyr	synonymous	Exon 3 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.255C>T	p.Tyr85Tyr	synonymous	Exon 4 of 11	NP_001129509.2	Q7Z4I7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.189C>T	p.Tyr63Tyr	synonymous	Exon 3 of 10	ENSP00000347240.4	Q7Z4I7-1
	LIMS2	ENST00000324938.9	TSL:1	c.261C>T	p.Tyr87Tyr	synonymous	Exon 3 of 10	ENSP00000326888.5	Q7Z4I7-2
	LIMS2	ENST00000409455.5	TSL:1	c.174C>T	p.Tyr58Tyr	synonymous	Exon 3 of 10	ENSP00000386383.1	Q7Z4I7-3

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3277 AN: 152226 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0181

GnomAD2 exomes AF: 0.0138 AC: 3458 AN: 250704 AF XY: 0.0135

Gnomad AFR exome AF: 0.0427

Gnomad AMR exome AF: 0.00753

Gnomad ASJ exome AF: 0.00488

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0156

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.0160 AC: 23316 AN: 1461674 Hom.: 221 Cov.: 31 AF XY: 0.0158 AC XY: 11493 AN XY: 727132

African (AFR) AF: 0.0452 AC: 1512 AN: 33478

American (AMR) AF: 0.00758 AC: 339 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00474 AC: 124 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0110 AC: 948 AN: 86248

European-Finnish (FIN) AF: 0.0122 AC: 649 AN: 53364

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5768

European-Non Finnish (NFE) AF: 0.0169 AC: 18756 AN: 1111882

Other (OTH) AF: 0.0152 AC: 918 AN: 60386

GnomAD4 genome AF: 0.0215 AC: 3280 AN: 152344 Hom.: 54 Cov.: 33 AF XY: 0.0206 AC XY: 1536 AN XY: 74504

African (AFR) AF: 0.0425 AC: 1766 AN: 41572

American (AMR) AF: 0.00830 AC: 127 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4826

European-Finnish (FIN) AF: 0.0137 AC: 146 AN: 10628

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1131 AN: 68034

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Alfa AF: 0.0171 Hom.: 54

Bravo AF: 0.0214

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0156

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2W (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.8
DANN	Benign	0.82
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35765118; hg19: chr2-128412453;