2-127639361-G-A

Variant names:

• chr2-127639361-G-A
• rs1454700502
• NM_001161403.3:c.946C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001161403.3(LIMS2):​c.946C>T​(p.Leu316Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.88
• 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

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=-0.32).
• BP6: Variant 2-127639361-G-A is Benign according to our data. Variant chr2-127639361-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2049681.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161403.3. 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
	LIMS2	NM_001161403.3	MANE Select	c.946C>T	p.Leu316Leu	synonymous	Exon 10 of 10	NP_001154875.1	Q7Z4I7-1
	LIMS2	NM_017980.5		c.1018C>T	p.Leu340Leu	synonymous	Exon 10 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.1012C>T	p.Leu338Leu	synonymous	Exon 11 of 11	NP_001129509.2	Q7Z4I7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.946C>T	p.Leu316Leu	synonymous	Exon 10 of 10	ENSP00000347240.4	Q7Z4I7-1
	LIMS2	ENST00000324938.9	TSL:1	c.1018C>T	p.Leu340Leu	synonymous	Exon 10 of 10	ENSP00000326888.5	Q7Z4I7-2
	LIMS2	ENST00000409455.5	TSL:1	c.931C>T	p.Leu311Leu	synonymous	Exon 10 of 10	ENSP00000386383.1	Q7Z4I7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461720 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2W (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		5.9
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: rs1454700502; hg19: chr2-128396936;