Genetic Variant NM_001161403.3:c.594C>T (chr2-127642115-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4BP6_ModerateBP7BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.793

Publications

1 publications found

Variant links:

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)

LIMS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMS2	NM_001161403.3 link	c.594C>T	p.Cys198Cys	synonymous_variant	Exon 6 of 10	ENST00000355119.9	NP_001154875.1	Q7Z4I7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9 link	c.594C>T	p.Cys198Cys	synonymous_variant	Exon 6 of 10	1	NM_001161403.3	ENSP00000347240.4		Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

393

AN:

152212

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.000341

AC XY:

247

AN XY:

723492

show subpopulations

African (AFR)

AF:

0.0107

AC:

357

AN:

33380

American (AMR)

AF:

0.000925

AC:

AN:

44306

Ashkenazi Jewish (ASJ)

AF:

0.000231

AC:

AN:

25998

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39498

South Asian (SAS)

AF:

0.0000351

AC:

AN:

85490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51880

Middle Eastern (MID)

AF:

0.00210

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000622

AC:

AN:

1109144

Other (OTH)

AF:

0.000816

AC:

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00257

AC:

392

AN:

152330

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00852

AC:

354

AN:

41570

American (AMR)

AF:

0.00150

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68020

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000871

Hom.:

Bravo

AF:

0.00302

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2W

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.73

CADD

Benign

0.73

(source)

DANN

Benign

0.94

PhyloP100

-0.79

PromoterAI

-0.00060

Neutral

(source)

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over