chr19-51380473-G-A

Position:

• chr19-51380473-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.251

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1274050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIM2	NM_001161748.2	c.460+32C>T		intron_variant		ENST00000596399.2
LIM2	NM_030657.4	c.586+32C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIM2	ENST00000596399.2	c.460+32C>T		intron_variant		1	NM_001161748.2	P1
LIM2	ENST00000221973.7	c.586+32C>T		intron_variant		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

GnomAD3 exomes AF: 0.726 AC: 182200 AN: 251094 Hom.: 66863 AF XY: 0.717 AC XY: 97312 AN XY: 135700

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 SAS exome AF: 0.660

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

Gnomad4 AFR exome AF: 0.953

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.660

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.724

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

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.731

Gnomad4 OTH AF: 0.774

Alfa AF: 0.722 Hom.: 67607

Bravo AF: 0.788

Asia WGS AF: 0.686 AC: 2390 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

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