Variant chr2-127640307-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001161403.3(LIMS2):c.765C>A(p.Asp255Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LIMS2
NM_001161403.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.632

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMS2	NM_001161403.3 linkuse as main transcript	c.765C>A	p.Asp255Glu	missense_variant	8/10	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.765C>A	p.Asp255Glu	missense_variant	8/10	1	NM_001161403.3	ENSP00000347240.4		Q7Z4I7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249622

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.837C>A (p.D279E) alteration is located in exon 8 (coding exon 8) of the LIMS2 gene. This alteration results from a C to A substitution at nucleotide position 837, causing the aspartic acid (D) at amino acid position 279 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

4.5

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

.;.;.;.;T;.;.;.;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.96

.;.;D;.;D;.;D;.;D;D

M_CAP

Benign

0.070

MetaRNN

Uncertain

0.51

D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.13

.;.;.;.;N;.;.;.;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.4

N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.59

Sift

Benign

0.13

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.62

T;T;T;T;T;T;T;T;T;T

Polyphen

1.0, 1.0

.;.;D;.;D;.;.;.;.;.

Vest4

0.73

MutPred

0.50

.;.;.;.;Gain of catalytic residue at D255 (P = 0.2318);.;.;.;.;.;

MVP

0.72

MPC

0.52

ClinPred

0.34

GERP RS

-2.5

Varity_R

0.13

gMVP

0.25

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

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