rs149101001

Positions:

• chr2-127639425-G-C
• chr2-127639425-G-T

Variant summary

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

The NM_001161403.3(LIMS2):​c.882C>G​(p.Asn294Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LIMS2 NM_001161403.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

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]

ACMG classification

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	UniProt
LIMS2	NM_001161403.3	c.882C>G	p.Asn294Lys	missense_variant	10/10	ENST00000355119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMS2	ENST00000355119.9	c.882C>G	p.Asn294Lys	missense_variant	10/10	1	NM_001161403.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2W Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.067
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.047	D;D;T;D;D;D;D;D;T;D
Sift4G	Benign	0.22	T;T;T;T;T;T;T;T;T;T
Polyphen		1.0, 1.0	.;.;D;.;D;.;.;.;.;.
Vest4		0.54
MutPred		0.60		.;.;.;.;Gain of methylation at N294 (P = 0.0247);.;.;.;.;.;
MVP		0.87
MPC		0.57
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.23
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.90		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.90		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149101001; hg19: chr2-128397000;