rs143117627

Variant names:

• chr2-127657535-G-A
• rs143117627
• NM_001161403.3:c.39C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-127657535-G-A
• chr2-127657535-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001161403.3(LIMS2):​c.39C>T​(p.Ala13Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,609,554 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (14 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.49
• Publications: 1 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-127657535-G-A is Benign according to our data. Variant chr2-127657535-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR,Unknown gene

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.39C>T	p.Ala13Ala	synonymous	Exon 2 of 10	NP_001154875.1	Q7Z4I7-1
	LIMS2	NM_017980.5		c.111C>T	p.Ala37Ala	synonymous	Exon 2 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.105C>T	p.Ala35Ala	synonymous	Exon 3 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.39C>T	p.Ala13Ala	synonymous	Exon 2 of 10	ENSP00000347240.4	Q7Z4I7-1
	LIMS2	ENST00000324938.9	TSL:1	c.111C>T	p.Ala37Ala	synonymous	Exon 2 of 10	ENSP00000326888.5	Q7Z4I7-2
	LIMS2	ENST00000409455.5	TSL:1	c.24C>T	p.Ala8Ala	synonymous	Exon 2 of 10	ENSP00000386383.1	Q7Z4I7-3

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 283 AN: 152260 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00214 AC: 526 AN: 245772 AF XY: 0.00209

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.0227

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00318

GnomAD4 exome AF: 0.00207 AC: 3011 AN: 1457176 Hom.: 14 Cov.: 31 AF XY: 0.00203 AC XY: 1471 AN XY: 724632

African (AFR) AF: 0.000239 AC: 8 AN: 33464

American (AMR) AF: 0.00144 AC: 64 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.0229 AC: 590 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000549 AC: 47 AN: 85624

European-Finnish (FIN) AF: 0.000210 AC: 11 AN: 52338

Middle Eastern (MID) AF: 0.00472 AC: 27 AN: 5716

European-Non Finnish (NFE) AF: 0.00186 AC: 2060 AN: 1109842

Other (OTH) AF: 0.00339 AC: 204 AN: 60236

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152378 Hom.: 1 Cov.: 33 AF XY: 0.00170 AC XY: 127 AN XY: 74510

African (AFR) AF: 0.000553 AC: 23 AN: 41588

American (AMR) AF: 0.00255 AC: 39 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00191 AC: 130 AN: 68038

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00301 Hom.: 3

Bravo AF: 0.00216

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2W (1)
-	-	1	LIMS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.51
DANN	Benign	0.90
PhyloP100		-1.5
Mutation Taster		=95/5	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: rs143117627; hg19: chr2-128415109;