rs754385302

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001161403.3(LIMS2):ā€‹c.276C>Gā€‹(p.Asn92Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000768 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.000082 ( 0 hom. )

Consequence

LIMS2
NM_001161403.3 missense

Scores

4
12
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.879
BS2
High AC in GnomAdExome4 at 120 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIMS2NM_001161403.3 linkc.276C>G p.Asn92Lys missense_variant 4/10 ENST00000355119.9 NP_001154875.1 Q7Z4I7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LIMS2ENST00000355119.9 linkc.276C>G p.Asn92Lys missense_variant 4/101 NM_001161403.3 ENSP00000347240.4 Q7Z4I7-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251412
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000821
AC:
120
AN:
1461816
Hom.:
0
Cov.:
33
AF XY:
0.0000756
AC XY:
55
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Benign
0.0091
T
BayesDel_noAF
Benign
-0.090
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
.;.;D;.;.;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;.;D;.;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.88
D;D;D;D;D;D
MetaSVM
Uncertain
0.76
D
MutationAssessor
Uncertain
2.3
.;.;M;.;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-4.2
D;D;D;D;D;D
REVEL
Pathogenic
0.67
Sift
Uncertain
0.0030
D;D;D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;.;.
Vest4
0.85
MutPred
0.67
.;.;Gain of catalytic residue at N92 (P = 0.0271);.;.;.;
MVP
0.98
MPC
0.44
ClinPred
0.92
D
GERP RS
4.5
Varity_R
0.67
gMVP
0.63

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.

Other links and lift over

dbSNP: rs754385302; hg19: chr2-128412081; API