NM_001161748.2:c.461-11T>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001161748.2(LIM2):​c.461-11T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,612,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LIM2
NM_001161748.2 intron

Scores

2
Splicing: ADA: 0.002881
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.811
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIM2NM_001161748.2 linkc.461-11T>G intron_variant Intron 4 of 4 ENST00000596399.2 NP_001155220.1 P55344-1
LIM2NM_030657.4 linkc.587-11T>G intron_variant Intron 4 of 4 NP_085915.2 P55344-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIM2ENST00000596399.2 linkc.461-11T>G intron_variant Intron 4 of 4 1 NM_001161748.2 ENSP00000472090.2 P55344-1
LIM2ENST00000221973.7 linkc.587-11T>G intron_variant Intron 4 of 4 1 ENSP00000221973.2 P55344-2

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152078
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000732
AC:
18
AN:
245764
Hom.:
0
AF XY:
0.0000375
AC XY:
5
AN XY:
133212
show subpopulations
Gnomad AFR exome
AF:
0.0000627
Gnomad AMR exome
AF:
0.000117
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000109
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000137
AC:
200
AN:
1460826
Hom.:
0
Cov.:
31
AF XY:
0.000120
AC XY:
87
AN XY:
726580
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000897
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000168
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000658
AC:
10
AN:
152078
Hom.:
0
Cov.:
31
AF XY:
0.0000539
AC XY:
4
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000693
Hom.:
0
Bravo
AF:
0.0000718

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cataract 19 multiple types Uncertain:1
May 20, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change falls in intron 4 of the LIM2 gene. It does not directly change the encoded amino acid sequence of the LIM2 protein. This variant is present in population databases (rs201548193, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LIM2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
9.8
DANN
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0029
dbscSNV1_RF
Benign
0.15
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201548193; hg19: chr19-51883527; API