2-127643047-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000409754.5(LIMS2):c.-72C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00515 in 1,585,184 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0051 ( 27 hom. )

Consequence

LIMS2
ENST00000409754.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.49

Publications

8 publications found

Variant links:

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]

LIMS2 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2W
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

LIMS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009791315).

BP6

Variant 2-127643047-G-A is Benign according to our data. Variant chr2-127643047-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMS2	NM_001161403.3 link	c.385C>T	p.Arg129Cys	missense_variant	Exon 5 of 10	ENST00000355119.9	NP_001154875.1	Q7Z4I7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9 link	c.385C>T	p.Arg129Cys	missense_variant	Exon 5 of 10	1	NM_001161403.3	ENSP00000347240.4		Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

847

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00572

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00504

AC:

1017

AN:

201794

AF XY:

0.00513

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.000220

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00555

Gnomad OTH exome

AF:

0.00367

GnomAD4 exome

AF:

0.00510

AC:

7307

AN:

1432808

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

3696

AN XY:

710014

show subpopulations

African (AFR)

AF:

0.00682

AC:

225

AN:

32998

American (AMR)

AF:

0.00151

AC:

AN:

40380

Ashkenazi Jewish (ASJ)

AF:

0.0000783

AC:

AN:

25552

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38266

South Asian (SAS)

AF:

0.00647

AC:

530

AN:

81902

European-Finnish (FIN)

AF:

0.0129

AC:

650

AN:

50414

Middle Eastern (MID)

AF:

0.00301

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00509

AC:

5593

AN:

1098360

Other (OTH)

AF:

0.00385

AC:

228

AN:

59296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

413

826

1238

1651

2064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00557

AC:

849

AN:

152376

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

412

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00639

AC:

266

AN:

41596

American (AMR)

AF:

0.00235

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00497

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0112

AC:

119

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00572

AC:

389

AN:

68040

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00532

Hom.:

Bravo

AF:

0.00478

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00843

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00483

AC:

579

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LIMS2: BS2 -

LIMS2-related disorder

Benign:1

Jul 10, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Autosomal recessive limb-girdle muscular dystrophy type 2W

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

.;.;D;.;.;.

Eigen

Benign

0.085

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;.;D;.;D;D

MetaRNN

Benign

0.0098

T;T;T;T;T;T

MetaSVM

Uncertain

0.65

MutationAssessor

Pathogenic

3.4

.;.;M;.;.;.

PhyloP100

4.5

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.1

D;D;D;D;D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.0050

D;D;D;D;D;D

Sift4G

Uncertain

0.046

D;D;D;D;D;D

Polyphen

0.010

B;.;B;.;.;.

Vest4

0.63

MVP

0.90

MPC

0.50

ClinPred

0.031

GERP RS

4.4

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.50

gMVP

0.62

Mutation Taster

=291/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over