NM_001161403.3:c.399G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001161403.3(LIMS2):c.399G>A(p.Lys133Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,585,692 control chromosomes in the GnomAD database, including 229,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21321 hom., cov: 35)

Exomes 𝑓: 0.54 ( 208238 hom. )

Consequence

LIMS2
NM_001161403.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.633

Publications

13 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-127643033-C-T is Benign according to our data. Variant chr2-127643033-C-T is described in ClinVar as Benign. ClinVar VariationId is 260987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.633 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMS2	NM_001161403.3 link	c.399G>A	p.Lys133Lys	synonymous_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.399G>A	p.Lys133Lys	synonymous_variant	Exon 5 of 10	1	NM_001161403.3	ENSP00000347240.4		Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79872

AN:

152026

Hom.:

21306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.535

GnomAD2 exomes

AF:

0.557

AC:

114041

AN:

204722

AF XY:

0.544

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.726

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.523

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.535

AC:

767440

AN:

1433546

Hom.:

208238

Cov.:

AF XY:

0.532

AC XY:

377990

AN XY:

710416

show subpopulations

African (AFR)

AF:

0.469

AC:

15477

AN:

32988

American (AMR)

AF:

0.715

AC:

29049

AN:

40616

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

15533

AN:

25576

East Asian (EAS)

AF:

0.755

AC:

28986

AN:

38370

South Asian (SAS)

AF:

0.451

AC:

36977

AN:

82026

European-Finnish (FIN)

AF:

0.531

AC:

26911

AN:

50720

Middle Eastern (MID)

AF:

0.551

AC:

3127

AN:

5678

European-Non Finnish (NFE)

AF:

0.527

AC:

579338

AN:

1098284

Other (OTH)

AF:

0.540

AC:

32042

AN:

59288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19514

39027

58541

78054

97568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16760

33520

50280

67040

83800

<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:

0.525

AC:

79908

AN:

152146

Hom.:

21321

Cov.:

AF XY:

0.526

AC XY:

39135

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.468

AC:

19425

AN:

41512

American (AMR)

AF:

0.615

AC:

9397

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2143

AN:

3470

East Asian (EAS)

AF:

0.707

AC:

3656

AN:

5174

South Asian (SAS)

AF:

0.453

AC:

2186

AN:

4822

European-Finnish (FIN)

AF:

0.534

AC:

5654

AN:

10590

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35617

AN:

67970

Other (OTH)

AF:

0.529

AC:

1118

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2023

4046

6069

8092

10115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.530

Hom.:

10067

Bravo

AF:

0.534

Asia WGS

AF:

0.553

AC:

1929

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive limb-girdle muscular dystrophy type 2W

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.63

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=93/7

polymorphism (auto)

(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