NM_001161403.3:c.*49T>C

Variant names:

• chr2-127639232-A-G
• rs891515
• NM_001161403.3:c.*49T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.500
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy type 2W

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1257147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161403.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	NM_001161403.3	MANE Select	c.*49T>C		3_prime_UTR	Exon 10 of 10	NP_001154875.1	Q7Z4I7-1
	LIMS2	NM_017980.5		c.*49T>C		3_prime_UTR	Exon 10 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.*49T>C		3_prime_UTR	Exon 11 of 11	NP_001129509.2	Q7Z4I7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.*49T>C		3_prime_UTR	Exon 10 of 10	ENSP00000347240.4	Q7Z4I7-1
	LIMS2	ENST00000324938.9	TSL:1	c.*49T>C		3_prime_UTR	Exon 10 of 10	ENSP00000326888.5	Q7Z4I7-2
	LIMS2	ENST00000409455.5	TSL:1	c.*49T>C		3_prime_UTR	Exon 10 of 10	ENSP00000386383.1	Q7Z4I7-3

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

GnomAD2 exomes AF: 0.521 AC: 125860 AN: 241786 AF XY: 0.532

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 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

African (AFR) AF: 0.801 AC: 26562 AN: 33156

American (AMR) AF: 0.376 AC: 16426 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 12761 AN: 25286

East Asian (EAS) AF: 0.271 AC: 10709 AN: 39482

South Asian (SAS) AF: 0.685 AC: 58151 AN: 84896

European-Finnish (FIN) AF: 0.566 AC: 29417 AN: 51946

Middle Eastern (MID) AF: 0.646 AC: 3487 AN: 5396

European-Non Finnish (NFE) AF: 0.501 AC: 551614 AN: 1101950

Other (OTH) AF: 0.522 AC: 31160 AN: 59706

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

African (AFR) AF: 0.787 AC: 32621 AN: 41424

American (AMR) AF: 0.468 AC: 7153 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1324 AN: 5142

South Asian (SAS) AF: 0.686 AC: 3302 AN: 4810

European-Finnish (FIN) AF: 0.567 AC: 5984 AN: 10546

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34635 AN: 67926

Other (OTH) AF: 0.571 AC: 1202 AN: 2106

Alfa AF: 0.530 Hom.: 11478

Bravo AF: 0.578

Asia WGS AF: 0.524 AC: 1824 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.28
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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