2-127654482-G-T

Variant names:

• chr2-127654482-G-T
• NM_001161403.3:c.301C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001161403.3(LIMS2):​c.301C>A​(p.Arg101Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIMS2 NM_001161403.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMS2	NM_001161403.3	c.301C>A	p.Arg101Ser	missense_variant	Exon 4 of 10	ENST00000355119.9	NP_001154875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMS2	ENST00000355119.9	c.301C>A	p.Arg101Ser	missense_variant	Exon 4 of 10	1	NM_001161403.3	ENSP00000347240.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	.;.;T;.;.;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;.;D;.;D;D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Benign	1.7	.;.;L;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.35	T;T;T;T;T;T
Sift4G	Benign	0.44	T;T;T;T;T;T
Polyphen		0.89	P;.;P;.;.;.
Vest4		0.68
MutPred		0.70		.;.;Loss of catalytic residue at R101 (P = 0.1661);.;.;.;
MVP		0.84
MPC		0.29
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.59
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-128412056;