Variant rs35765118 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000355119.9(LIMS2):c.189C>T(p.Tyr63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,614,018 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 54 hom., cov: 33)

Exomes 𝑓: 0.016 ( 221 hom. )

Consequence

LIMS2
ENST00000355119.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.82

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-127654879-G-A is Benign according to our data. Variant chr2-127654879-G-A is described in ClinVar as [Benign]. Clinvar id is 260984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127654879-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.82 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0215 (3280/152344) while in subpopulation AFR AF= 0.0425 (1766/41572). AF 95% confidence interval is 0.0408. There are 54 homozygotes in gnomad4. There are 1536 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMS2	NM_001161403.3 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/10	ENST00000355119.9	NP_001154875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9 linkuse as main transcript	c.189C>T	p.Tyr63=	synonymous_variant	3/10	1	NM_001161403.3	ENSP00000347240	P1	Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3277

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.0138

AC:

3458

AN:

250704

Hom.:

AF XY:

0.0135

AC XY:

1831

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.00753

Gnomad ASJ exome

AF:

0.00488

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0160

AC:

23316

AN:

1461674

Hom.:

221

Cov.:

AF XY:

0.0158

AC XY:

11493

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0452

Gnomad4 AMR exome

AF:

0.00758

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0215

AC:

3280

AN:

152344

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1536

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0425

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0155

EpiControl

AF:

0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive limb-girdle muscular dystrophy type 2W

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.8

DANN

Benign

0.82

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

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