Variant 2-127640153-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001161403.3(LIMS2):c.803-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,613,234 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 23 hom., cov: 33)

Exomes 𝑓: 0.018 ( 279 hom. )

Consequence

LIMS2
NM_001161403.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.02291

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.59

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-127640153-G-C is Benign according to our data. Variant chr2-127640153-G-C is described in ClinVar as [Benign]. Clinvar id is 260989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127640153-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.014 (2133/152348) while in subpopulation NFE AF= 0.02 (1358/68026). AF 95% confidence interval is 0.0191. There are 23 homozygotes in gnomad4. There are 989 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMS2	NM_001161403.3 linkuse as main transcript	c.803-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000355119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMS2	ENST00000355119.9 linkuse as main transcript	c.803-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001161403.3	P1	Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2132

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00437

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00734

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0141

AC:

3535

AN:

250628

Hom.:

AF XY:

0.0138

AC XY:

1873

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00346

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0349

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.00786

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0244

GnomAD4 exome

AF:

0.0177

AC:

25925

AN:

1460886

Hom.:

279

Cov.:

AF XY:

0.0177

AC XY:

12849

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.0372

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00477

Gnomad4 FIN exome

AF:

0.00806

Gnomad4 NFE exome

AF:

0.0199

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0140

AC:

2133

AN:

152348

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

989

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00435

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00734

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0150

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive limb-girdle muscular dystrophy type 2W

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.023

dbscSNV1_RF

Benign

0.26

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over