19-51387313-C-T

Position:

chr19-51387313-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001161748.2(LIM2):c.131G>A(p.Arg44Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

LIM2
NM_001161748.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.12

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:):

LIM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIM2	NM_001161748.2 linkuse as main transcript	c.131G>A	p.Arg44Gln	missense_variant	2/5	ENST00000596399.2	NP_001155220.1	P55344-1
LIM2	NM_030657.4 linkuse as main transcript	c.131G>A	p.Arg44Gln	missense_variant	2/5		NP_085915.2	P55344-2
LIM2-AS1	XR_002958397.2 linkuse as main transcript	n.116C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIM2	ENST00000596399.2 linkuse as main transcript	c.131G>A	p.Arg44Gln	missense_variant	2/5	1	NM_001161748.2	ENSP00000472090.2		P55344-1
LIM2	ENST00000221973.7 linkuse as main transcript	c.131G>A	p.Arg44Gln	missense_variant	2/5	1		ENSP00000221973.2		P55344-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251222

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000118

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

The c.131G>A (p.R44Q) alteration is located in exon 2 (coding exon 1) of the LIM2 gene. This alteration results from a G to A substitution at nucleotide position 131, causing the arginine (R) at amino acid position 44 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Cataract 19 multiple types

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

.;D

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

N;.

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0080

D;.

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.62

MVP

0.92

MPC

0.53

ClinPred

0.21

GERP RS

4.0

Varity_R

0.29

gMVP

0.81

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over