2-127639232-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001161403.3(LIMS2):c.*49T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,597,422 control chromosomes in the GnomAD database, including 222,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (27482 hom., cov: 32)
  • Exomes 𝑓: 0.51 (194948 hom.)
• Consequence: LIMS2 NM_001161403.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-127639232-A-G is Benign according to our data. Variant chr2-127639232-A-G is described in ClinVar as [Benign]. Clinvar id is 1257147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMS2	NM_001161403.3	c.*49T>C		3_prime_UTR_variant	10/10	ENST00000355119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMS2	ENST00000355119.9	c.*49T>C		3_prime_UTR_variant	10/10	1	NM_001161403.3	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88569 AN: 151788 Hom.: 27457 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.568

GnomAD3 exomes AF: 0.521 AC: 125860 AN: 241786 Hom.: 35084 AF XY: 0.532 AC XY: 69468 AN XY: 130622

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.692

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.518

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.512 AC: 740287 AN: 1445516 Hom.: 194948 Cov.: 30 AF XY: 0.518 AC XY: 371632 AN XY: 718068

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.583 AC: 88630 AN: 151906 Hom.: 27482 Cov.: 32 AF XY: 0.583 AC XY: 43291 AN XY: 74240

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.571

Alfa AF: 0.524 Hom.: 9651

Bravo AF: 0.578

Asia WGS AF: 0.524 AC: 1824 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.55
Dann	Benign	0.28

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: rs891515; hg19: chr2-128396807; COSMIC: COSV61444268; COSMIC: COSV61444268;