Variant chr2-127643033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001161403.3(LIMS2):c.399G>A(p.Lys133Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,585,692 control chromosomes in the GnomAD database, including 229,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21321 hom., cov: 35)

Exomes 𝑓: 0.54 ( 208238 hom. )

Consequence

LIMS2
NM_001161403.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.633

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 links:

LIMS2 (HGNC:):

LIMS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-127643033-C-T is Benign according to our data. Variant chr2-127643033-C-T is described in ClinVar as [Benign]. Clinvar id is 260987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127643033-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.633 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMS2	NM_001161403.3 linkuse as main transcript	c.399G>A	p.Lys133Lys	synonymous_variant	5/10	ENST00000355119.9	NP_001154875.1	Q7Z4I7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9 linkuse as main transcript	c.399G>A	p.Lys133Lys	synonymous_variant	5/10	1	NM_001161403.3	ENSP00000347240.4		Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79872

AN:

152026

Hom.:

21306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.535

GnomAD3 exomes

AF:

0.557

AC:

114041

AN:

204722

Hom.:

32657

AF XY:

0.544

AC XY:

59907

AN XY:

110032

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.726

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.695

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.523

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.535

AC:

767440

AN:

1433546

Hom.:

208238

Cov.:

AF XY:

0.532

AC XY:

377990

AN XY:

710416

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.715

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.755

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.531

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.525

AC:

79908

AN:

152146

Hom.:

21321

Cov.:

AF XY:

0.526

AC XY:

39135

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.615

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.707

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.524

Gnomad4 OTH

AF:

0.529

Alfa

AF:

0.530

Hom.:

10067

Bravo

AF:

0.534

Asia WGS

AF:

0.553

AC:

1929

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Autosomal recessive limb-girdle muscular dystrophy type 2W

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.85

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over