rs143117627

chr2-127657535-G-Achr2-127657535-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001161403.3(LIMS2):c.39C>T(p.Ala13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,609,554 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (14 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.49

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-127657535-G-A is Benign according to our data. Variant chr2-127657535-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BS2: High AC in GnomAd at 283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMS2	NM_001161403.3	c.39C>T	p.Ala13=	synonymous_variant	2/10	ENST00000355119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMS2	ENST00000355119.9	c.39C>T	p.Ala13=	synonymous_variant	2/10	1	NM_001161403.3	P1

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 283 AN: 152260 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00214 AC: 526 AN: 245772 Hom.: 6 AF XY: 0.00209 AC XY: 278 AN XY: 132972

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.0227

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000470

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00318

GnomAD4 exome AF: 0.00207 AC: 3011 AN: 1457176 Hom.: 14 Cov.: 31 AF XY: 0.00203 AC XY: 1471 AN XY: 724632

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000549

Gnomad4 FIN exome AF: 0.000210

Gnomad4 NFE exome AF: 0.00186

Gnomad4 OTH exome AF: 0.00339

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152378 Hom.: 1 Cov.: 33 AF XY: 0.00170 AC XY: 127 AN XY: 74510

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00301 Hom.: 3

Bravo AF: 0.00216

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

LIMS2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

LIMS2: BP4, BP7, BS2 -

Autosomal recessive limb-girdle muscular dystrophy type 2W Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.51
Dann	Benign	0.90

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: rs143117627; hg19: chr2-128415109;