chr2-127643076-C-A

Variant names:

• chr2-127643076-C-A
• rs112254310
• NM_001161403.3:c.360-4G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001161403.3(LIMS2):​c.360-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,568,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: LIMS2 NM_001161403.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002956
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.99
• Publications: 0 publications found

Genes affected

LIMS2 (HGNC:16084): (LIM zinc finger domain containing 2) This gene encodes a member of a small family of focal adhesion proteins which interacts with ILK (integrin-linked kinase), a protein which effects protein-protein interactions with the extraceullar matrix. The encoded protein has five LIM domains, each domain forming two zinc fingers, which permit interactions which regulate cell shape and migration. A pseudogene of this gene is located on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

LIMS2 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy type 2W

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-127643076-C-A is Benign according to our data. Variant chr2-127643076-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 665103.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMS2	NM_001161403.3	c.360-4G>T		splice_region_variant, intron_variant	Intron 4 of 9	ENST00000355119.9	NP_001154875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9	c.360-4G>T		splice_region_variant, intron_variant	Intron 4 of 9	1	NM_001161403.3	ENSP00000347240.4

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152234 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000962 AC: 17 AN: 176704 AF XY: 0.0000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000740

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 202 AN: 1416552 Hom.: 0 Cov.: 33 AF XY: 0.000136 AC XY: 95 AN XY: 700950

African (AFR) AF: 0.0000307 AC: 1 AN: 32582

American (AMR) AF: 0.0000261 AC: 1 AN: 38326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 37508

South Asian (SAS) AF: 0.00 AC: 0 AN: 80758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47584

Middle Eastern (MID) AF: 0.000193 AC: 1 AN: 5190

European-Non Finnish (NFE) AF: 0.000178 AC: 194 AN: 1090584

Other (OTH) AF: 0.0000852 AC: 5 AN: 58672

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152234 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2W Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.068
DANN	Benign	0.75
PhyloP100		-3.0
PromoterAI		0.0066	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.16
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: rs112254310; hg19: chr2-128400651;