rs968524490

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_017980.5(LIMS2):c.79A>G(p.Thr27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000488 in 1,233,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T27S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

LIMS2
NM_017980.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.315

Publications

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

LIMS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03418675).

BP6

Variant 2-127664310-T-C is Benign according to our data. Variant chr2-127664310-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 571615.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017980.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIMS2	NM_001161403.3	MANE Select	c.12-6748A>G		intron	N/A	NP_001154875.1	Q7Z4I7-1
LIMS2	NM_017980.5		c.79A>G	p.Thr27Ala	missense	Exon 1 of 10	NP_060450.2
LIMS2	NM_001136037.4		c.78-6748A>G		intron	N/A	NP_001129509.2	Q7Z4I7-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIMS2	ENST00000324938.9	TSL:1	c.79A>G	p.Thr27Ala	missense	Exon 1 of 10	ENSP00000326888.5	Q7Z4I7-2
LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.12-6748A>G		intron	N/A	ENSP00000347240.4	Q7Z4I7-1
LIMS2	ENST00000409455.5	TSL:1	c.-4-6748A>G		intron	N/A	ENSP00000386383.1	Q7Z4I7-3

Frequencies

GnomAD3 genomes

AF:

0.000402

AC:

AN:

151690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000810

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.00

AC:

AN:

4094

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000500

AC:

541

AN:

1081530

Hom.:

Cov.:

AF XY:

0.000539

AC XY:

277

AN XY:

514030

show subpopulations

African (AFR)

AF:

0.0000894

AC:

AN:

22382

American (AMR)

AF:

0.00

AC:

AN:

8664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14132

East Asian (EAS)

AF:

0.00

AC:

AN:

25580

South Asian (SAS)

AF:

0.0000450

AC:

AN:

22232

European-Finnish (FIN)

AF:

0.0000467

AC:

AN:

21434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2876

European-Non Finnish (NFE)

AF:

0.000570

AC:

525

AN:

921184

Other (OTH)

AF:

0.000279

AC:

AN:

43046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000402

AC:

AN:

151690

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

74082

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41398

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000810

AC:

AN:

67860

Other (OTH)

AF:

0.000481

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000529

Hom.:

Bravo

AF:

0.000351

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive limb-girdle muscular dystrophy type 2W (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

(source)

DANN

Benign

0.26

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.094

M_CAP

Benign

0.016

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.97

PhyloP100

-0.32

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.19

REVEL

Benign

0.0050

Sift

Benign

0.76

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.037

MutPred

0.35

Loss of glycosylation at T27 (P = 0.008)

MVP

0.030

MPC

0.10

ClinPred

0.040

GERP RS

-1.7

PromoterAI

-0.049

Neutral

(source)

gMVP

0.31

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over