2-127643033-C-G

Position:

• chr2-127643033-C-G

Variant summary

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

The NM_001161403.3(LIMS2):​c.399G>C​(p.Lys133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,433,970 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K133K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LIMS2 NM_001161403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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 (HGNC:):

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	Protein	UniProt
LIMS2	NM_001161403.3	c.399G>C	p.Lys133Asn	missense_variant	5/10	ENST00000355119.9	NP_001154875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9	c.399G>C	p.Lys133Asn	missense_variant	5/10	1	NM_001161403.3	ENSP00000347240.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1433970 Hom.: 0 Cov.: 54 AF XY: 0.00000141 AC XY: 1 AN XY: 710666

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: 0.00

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;.;T;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;.;D;.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;.;L;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.18	T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.87	P;.;P;.;.;.
Vest4		0.44
MutPred		0.42		.;.;Loss of MoRF binding (P = 0.0527);.;.;.;
MVP		0.37
MPC		0.45
ClinPred		0.88	D
GERP RS		4.6
Varity_R		0.28
gMVP		0.47

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

Other links and lift over

dbSNP: rs4662751; hg19: chr2-128400608;