rs8111243

Variant names:

• chr19-51382512-G-A
• rs8111243
• NM_001161748.2:c.231C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51382512-G-A
• chr19-51382512-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -4.23
• Publications: 4 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 -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 VariationId is 329974.
• 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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 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.231C>T	p.Ser77Ser	synonymous	Exon 3 of 5	NP_001155220.1	P55344-1
	LIM2	NM_030657.4		c.357C>T	p.Ser119Ser	synonymous	Exon 3 of 5	NP_085915.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIM2	ENST00000596399.2	TSL:1 MANE Select	c.231C>T	p.Ser77Ser	synonymous	Exon 3 of 5	ENSP00000472090.2	P55344-1
	LIM2	ENST00000221973.7	TSL:1	c.357C>T	p.Ser119Ser	synonymous	Exon 3 of 5	ENSP00000221973.2	P55344-2
	LIM2	ENST00000853599.1		c.231C>T	p.Ser77Ser	synonymous	Exon 3 of 5	ENSP00000523658.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1793 AN: 152038 Hom.: 19 Cov.: 30

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

GnomAD2 exomes AF: 0.00721 AC: 1813 AN: 251392 AF XY: 0.00678

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 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.: 64 Cov.: 33 AF XY: 0.00785 AC XY: 5705 AN XY: 727182

African (AFR) AF: 0.0283 AC: 947 AN: 33476

American (AMR) AF: 0.00646 AC: 289 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 356 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00192 AC: 166 AN: 86252

European-Finnish (FIN) AF: 0.00569 AC: 304 AN: 53418

Middle Eastern (MID) AF: 0.00695 AC: 40 AN: 5754

European-Non Finnish (NFE) AF: 0.00825 AC: 9175 AN: 1111916

Other (OTH) AF: 0.00868 AC: 524 AN: 60380

GnomAD4 genome AF: 0.0118 AC: 1798 AN: 152156 Hom.: 19 Cov.: 30 AF XY: 0.0115 AC XY: 859 AN XY: 74388

African (AFR) AF: 0.0244 AC: 1011 AN: 41498

American (AMR) AF: 0.00844 AC: 129 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4830

European-Finnish (FIN) AF: 0.00406 AC: 43 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00774 AC: 526 AN: 67984

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.0101 Hom.: 16

Bravo AF: 0.0133

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00714

EpiControl AF: 0.00711

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	Cataract 19 multiple types (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		-4.2
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs8111243; hg19: chr19-51885766;