rs35765118

chr2-127654879-G-Achr2-127654879-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001161403.3(LIMS2):c.189C>T(p.Tyr63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,614,018 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (54 hom., cov: 33)
  • Exomes 𝑓: 0.016 (221 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.82

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 2-127654879-G-A is Benign according to our data. Variant chr2-127654879-G-A is described in ClinVar as [Benign]. Clinvar id is 260984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127654879-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0215 (3280/152344) while in subpopulation AFR AF= 0.0425 (1766/41572). AF 95% confidence interval is 0.0408. There are 54 homozygotes in gnomad4. There are 1536 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 3277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMS2	NM_001161403.3	c.189C>T	p.Tyr63=	synonymous_variant	3/10	ENST00000355119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMS2	ENST00000355119.9	c.189C>T	p.Tyr63=	synonymous_variant	3/10	1	NM_001161403.3	P1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3277 AN: 152226 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0181

GnomAD3 exomes AF: 0.0138 AC: 3458 AN: 250704 Hom.: 39 AF XY: 0.0135 AC XY: 1831 AN XY: 135770

Gnomad AFR exome AF: 0.0427

Gnomad AMR exome AF: 0.00753

Gnomad ASJ exome AF: 0.00488

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0113

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0156

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.0160 AC: 23316 AN: 1461674 Hom.: 221 Cov.: 31 AF XY: 0.0158 AC XY: 11493 AN XY: 727132

Gnomad4 AFR exome AF: 0.0452

Gnomad4 AMR exome AF: 0.00758

Gnomad4 ASJ exome AF: 0.00474

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.0122

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0215 AC: 3280 AN: 152344 Hom.: 54 Cov.: 33 AF XY: 0.0206 AC XY: 1536 AN XY: 74504

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0181 Hom.: 27

Bravo AF: 0.0214

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	8.8
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35765118; hg19: chr2-128412453;