19-51380516-G-C

Variant names:

• chr19-51380516-G-C
• rs747800845
• NM_001161748.2:c.449C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001161748.2(LIM2):​c.449C>G​(p.Thr150Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LIM2 NM_001161748.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIM2	NM_001161748.2	c.449C>G	p.Thr150Arg	missense_variant	Exon 4 of 5	ENST00000596399.2	NP_001155220.1
LIM2	NM_030657.4	c.575C>G	p.Thr192Arg	missense_variant	Exon 4 of 5		NP_085915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIM2	ENST00000596399.2	c.449C>G	p.Thr150Arg	missense_variant	Exon 4 of 5	1	NM_001161748.2	ENSP00000472090.2
LIM2	ENST00000221973.7	c.575C>G	p.Thr192Arg	missense_variant	Exon 4 of 5	1		ENSP00000221973.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.96	.;D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;D
Vest4		0.82
MutPred		0.87		.;Gain of MoRF binding (P = 0.0099);
MVP		0.98
MPC		0.50
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.68
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs747800845; hg19: chr19-51883770;