Genetic Variant LIM2:p.Leu19Leu (chr19-51387387-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001161748.2(LIM2):c.57G>A(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,188 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

LIM2
NM_001161748.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 1.81

Publications

3 publications found

Variant links:

Genes affected

LIM2 (HGNC:6610): (lens intrinsic membrane protein 2) This gene encodes an eye lens-specific protein found at the junctions of lens fiber cells, where it may contribute to cell junctional organization. It acts as a receptor for calmodulin, and may play an important role in both lens development and cataractogenesis. Mutations in this gene have been associated with cataract formation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

LIM2 links:

LIM2-AS1 (HGNC:56004): (LIM2 and SIGLEC10 antisense RNA 1)

LIM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 19-51387387-C-T is Benign according to our data. Variant chr19-51387387-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 541269.

BP7

Synonymous conserved (PhyloP=1.81 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161748.2. 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
	LIM2	NM_001161748.2	MANE Select	c.57G>A	p.Leu19Leu	synonymous	Exon 2 of 5	NP_001155220.1	P55344-1
	LIM2	NM_030657.4		c.57G>A	p.Leu19Leu	synonymous	Exon 2 of 5	NP_085915.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIM2	ENST00000596399.2	TSL:1 MANE Select	c.57G>A	p.Leu19Leu	synonymous	Exon 2 of 5	ENSP00000472090.2	P55344-1
LIM2	ENST00000221973.7	TSL:1	c.57G>A	p.Leu19Leu	synonymous	Exon 2 of 5	ENSP00000221973.2	P55344-2
LIM2	ENST00000853599.1		c.57G>A	p.Leu19Leu	synonymous	Exon 2 of 5	ENSP00000523658.1

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

113

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00751

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00101

AC:

255

AN:

251268

AF XY:

0.000920

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00772

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000801

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00110

AC:

1601

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

776

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26136

East Asian (EAS)

AF:

0.0145

AC:

575

AN:

39700

South Asian (SAS)

AF:

0.000371

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000937

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000868

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000841

AC:

935

AN:

1112008

Other (OTH)

AF:

0.000563

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

107

214

322

429

536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.000742

AC:

113

AN:

152346

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41590

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00753

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000732

Hom.:

Bravo

AF:

0.000854

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 19 multiple types (2)

Inborn genetic diseases (1)

LIM2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.8

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over