rs8111243

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001161748.2(LIM2):c.231C>T(p.Ser77Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00843 in 1,613,904 control chromosomes in the GnomAD database, including 83 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 0.012 ( 19 hom., cov: 30)

Exomes 𝑓: 0.0081 ( 64 hom. )

Consequence

LIM2
NM_001161748.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -4.23

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 19-51382512-G-A is Benign according to our data. Variant chr19-51382512-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 329974.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.

BP7

Synonymous conserved (PhyloP=-4.23 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1798/152156) while in subpopulation AFR AF= 0.0244 (1011/41498). AF 95% confidence interval is 0.0231. There are 19 homozygotes in gnomad4. There are 859 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIM2	NM_001161748.2 link	c.231C>T	p.Ser77Ser	synonymous_variant	3/5	ENST00000596399.2	NP_001155220.1	P55344-1
LIM2	NM_030657.4 link	c.357C>T	p.Ser119Ser	synonymous_variant	3/5		NP_085915.2	P55344-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIM2	ENST00000596399.2 link	c.231C>T	p.Ser77Ser	synonymous_variant	3/5	1	NM_001161748.2	ENSP00000472090.2		P55344-1
LIM2	ENST00000221973.7 link	c.357C>T	p.Ser119Ser	synonymous_variant	3/5	1		ENSP00000221973.2		P55344-2

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1793

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00406

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00774

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00721

AC:

1813

AN:

251392

Hom.:

AF XY:

0.00678

AC XY:

921

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00225

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.00722

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00807

AC:

11802

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

5705

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.00646

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.00569

Gnomad4 NFE exome

AF:

0.00825

Gnomad4 OTH exome

AF:

0.00868

GnomAD4 genome

AF:

0.0118

AC:

1798

AN:

152156

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

859

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0244

Gnomad4 AMR

AF:

0.00844

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00406

Gnomad4 NFE

AF:

0.00774

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00866

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00714

EpiControl

AF:

0.00711

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Cataract 19 multiple types

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -
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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

DANN

Benign

0.69

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