NM_001161403.3:c.*689T>G

Variant names:

• chr2-127638592-A-C
• rs78022502
• NM_001161403.3:c.*689T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161403.3(LIMS2):​c.*689T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,812 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.055 (264 hom., cov: 33)
  • Exomes 𝑓: 0.058 (4 hom.)
• Consequence: LIMS2 NM_001161403.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 11 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0644 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	NM_001161403.3	MANE Select	c.*689T>G		3_prime_UTR	Exon 10 of 10	NP_001154875.1
	LIMS2	NM_017980.5		c.*689T>G		3_prime_UTR	Exon 10 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.*689T>G		3_prime_UTR	Exon 11 of 11	NP_001129509.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.*689T>G		3_prime_UTR	Exon 10 of 10	ENSP00000347240.4
	LIMS2	ENST00000324938.9	TSL:1	c.*689T>G		3_prime_UTR	Exon 10 of 10	ENSP00000326888.5
	LIMS2	ENST00000409455.5	TSL:1	c.*689T>G		3_prime_UTR	Exon 10 of 10	ENSP00000386383.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8442 AN: 152162 Hom.: 265 Cov.: 33

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0583 AC: 31 AN: 532 Hom.: 4 Cov.: 0 AF XY: 0.0562 AC XY: 19 AN XY: 338

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.250 AC: 2 AN: 8

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.0556 AC: 1 AN: 18

European-Finnish (FIN) AF: 0.0180 AC: 4 AN: 222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0923 AC: 24 AN: 260

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0555 AC: 8450 AN: 152280 Hom.: 264 Cov.: 33 AF XY: 0.0536 AC XY: 3989 AN XY: 74460

African (AFR) AF: 0.0665 AC: 2763 AN: 41558

American (AMR) AF: 0.0644 AC: 985 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4828

European-Finnish (FIN) AF: 0.0336 AC: 357 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0571 AC: 3883 AN: 68016

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0566 Hom.: 42

Bravo AF: 0.0590

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		-0.61
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: rs78022502; hg19: chr2-128396167; COSMIC: COSV61442806; COSMIC: COSV61442806;