19-51379910-A-C

Variant names:

• chr19-51379910-A-C
• rs932195033
• NM_001161748.2:c.*291T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001161748.2(LIM2):​c.*291T>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 391,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: LIM2 NM_001161748.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.*291T>G		splice_region	Exon 5 of 5	NP_001155220.1	P55344-1
	LIM2	NM_001161748.2	MANE Select	c.*291T>G		3_prime_UTR	Exon 5 of 5	NP_001155220.1	P55344-1
	LIM2	NM_030657.4		c.*291T>G		splice_region	Exon 5 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.*291T>G		splice_region	Exon 5 of 5	ENSP00000472090.2	P55344-1
	LIM2	ENST00000221973.7	TSL:1	c.*291T>G		splice_region	Exon 5 of 5	ENSP00000221973.2	P55344-2
	LIM2	ENST00000596399.2	TSL:1 MANE Select	c.*291T>G		3_prime_UTR	Exon 5 of 5	ENSP00000472090.2	P55344-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000511 AC: 2 AN: 391634 Hom.: 0 Cov.: 0 AF XY: 0.00000486 AC XY: 1 AN XY: 205832

African (AFR) AF: 0.00 AC: 0 AN: 11362

American (AMR) AF: 0.000121 AC: 2 AN: 16530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12124

East Asian (EAS) AF: 0.00 AC: 0 AN: 26574

South Asian (SAS) AF: 0.00 AC: 0 AN: 41426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 234374

Other (OTH) AF: 0.00 AC: 0 AN: 22778

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
DANN	Benign	0.69
PhyloP100		-0.19

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: rs932195033; hg19: chr19-51883164;