NM_001161403.3:c.594C>T

Variant names:

• chr2-127642115-G-A
• rs74638847
• NM_001161403.3:c.594C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4 BP6_Moderate BP7 BS2

The NM_001161403.3(LIMS2):​c.594C>T​(p.Cys198Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000578 in 1,607,828 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.793
• 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.246).
• BP6: Variant 2-127642115-G-A is Benign according to our data. Variant chr2-127642115-G-A is described in ClinVar as Benign. ClinVar VariationId is 475548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.793 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 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.594C>T	p.Cys198Cys	synonymous	Exon 6 of 10	NP_001154875.1
	LIMS2	NM_017980.5		c.666C>T	p.Cys222Cys	synonymous	Exon 6 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.660C>T	p.Cys220Cys	synonymous	Exon 7 of 11	NP_001129509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.594C>T	p.Cys198Cys	synonymous	Exon 6 of 10	ENSP00000347240.4
	LIMS2	ENST00000324938.9	TSL:1	c.666C>T	p.Cys222Cys	synonymous	Exon 6 of 10	ENSP00000326888.5
	LIMS2	ENST00000409455.5	TSL:1	c.579C>T	p.Cys193Cys	synonymous	Exon 6 of 10	ENSP00000386383.1

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 393 AN: 152212 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00854

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000830 AC: 200 AN: 241000 AF XY: 0.000678

Gnomad AFR exome AF: 0.00945

Gnomad AMR exome AF: 0.000952

Gnomad ASJ exome AF: 0.000307

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.000686

GnomAD4 exome AF: 0.000370 AC: 538 AN: 1455498 Hom.: 1 Cov.: 30 AF XY: 0.000341 AC XY: 247 AN XY: 723492

African (AFR) AF: 0.0107 AC: 357 AN: 33380

American (AMR) AF: 0.000925 AC: 41 AN: 44306

Ashkenazi Jewish (ASJ) AF: 0.000231 AC: 6 AN: 25998

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39498

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51880

Middle Eastern (MID) AF: 0.00210 AC: 12 AN: 5726

European-Non Finnish (NFE) AF: 0.0000622 AC: 69 AN: 1109144

Other (OTH) AF: 0.000816 AC: 49 AN: 60076

GnomAD4 genome AF: 0.00257 AC: 392 AN: 152330 Hom.: 2 Cov.: 33 AF XY: 0.00243 AC XY: 181 AN XY: 74480

African (AFR) AF: 0.00852 AC: 354 AN: 41570

American (AMR) AF: 0.00150 AC: 23 AN: 15304

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68020

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000871 Hom.: 0

Bravo AF: 0.00302

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.73
CADD	Benign	0.73
DANN	Benign	0.94
PhyloP100		-0.79
PromoterAI		-0.00060	Neutral
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs74638847; hg19: chr2-128399690;