NM_001161748.2:c.460+32C>T

Variant names:

• chr19-51380473-G-A
• rs2547318
• NM_001161748.2:c.460+32C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161748.2(LIM2):​c.460+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,613,670 control chromosomes in the GnomAD database, including 437,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47482 hom., cov: 30)
  • Exomes 𝑓: 0.73 (389969 hom.)
• Consequence: LIM2 NM_001161748.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.251
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• cataract 19 multiple types

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-51380473-G-A is Benign according to our data. Variant chr19-51380473-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

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.460+32C>T		intron	N/A	NP_001155220.1	P55344-1
	LIM2	NM_030657.4		c.586+32C>T		intron	N/A	NP_085915.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIM2	ENST00000596399.2	TSL:1 MANE Select	c.460+32C>T		intron	N/A	ENSP00000472090.2	P55344-1
	LIM2	ENST00000221973.7	TSL:1	c.586+32C>T		intron	N/A	ENSP00000221973.2	P55344-2
	LIM2	ENST00000853599.1		c.460+32C>T		intron	N/A	ENSP00000523658.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118895 AN: 151876 Hom.: 47425 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.772

GnomAD2 exomes AF: 0.726 AC: 182200 AN: 251094 AF XY: 0.717

Gnomad AFR exome AF: 0.948

Gnomad AMR exome AF: 0.717

Gnomad ASJ exome AF: 0.619

Gnomad EAS exome AF: 0.674

Gnomad FIN exome AF: 0.737

Gnomad NFE exome AF: 0.731

Gnomad OTH exome AF: 0.709

GnomAD4 exome AF: 0.729 AC: 1065117 AN: 1461676 Hom.: 389969 Cov.: 48 AF XY: 0.725 AC XY: 527435 AN XY: 727158

African (AFR) AF: 0.953 AC: 31913 AN: 33480

American (AMR) AF: 0.716 AC: 32004 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 16089 AN: 26134

East Asian (EAS) AF: 0.708 AC: 28093 AN: 39698

South Asian (SAS) AF: 0.660 AC: 56908 AN: 86256

European-Finnish (FIN) AF: 0.735 AC: 39275 AN: 53416

Middle Eastern (MID) AF: 0.710 AC: 4098 AN: 5768

European-Non Finnish (NFE) AF: 0.731 AC: 813028 AN: 1111816

Other (OTH) AF: 0.724 AC: 43709 AN: 60386

GnomAD4 genome AF: 0.783 AC: 119014 AN: 151994 Hom.: 47482 Cov.: 30 AF XY: 0.780 AC XY: 57919 AN XY: 74276

African (AFR) AF: 0.943 AC: 39112 AN: 41472

American (AMR) AF: 0.723 AC: 11039 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2106 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3556 AN: 5152

South Asian (SAS) AF: 0.659 AC: 3169 AN: 4810

European-Finnish (FIN) AF: 0.745 AC: 7863 AN: 10552

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49711 AN: 67964

Other (OTH) AF: 0.774 AC: 1632 AN: 2108

Alfa AF: 0.727 Hom.: 92228

Bravo AF: 0.788

Asia WGS AF: 0.686 AC: 2390 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2547318; hg19: chr19-51883727; COSMIC: COSV55741911;