2-127664317-C-T

Variant names:

• chr2-127664317-C-T
• rs529824211
• ENST00000324938.9:c.72G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_017980.5(LIMS2):​c.72G>A​(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000836 in 1,232,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: LIMS2 NM_017980.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-127664317-C-T is Benign according to our data. Variant chr2-127664317-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 542254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017980.5. 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.12-6755G>A		intron	N/A	NP_001154875.1
	LIMS2	NM_017980.5		c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.78-6755G>A		intron	N/A	NP_001129509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000324938.9	TSL:1	c.72G>A	p.Pro24Pro	synonymous	Exon 1 of 10	ENSP00000326888.5
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.12-6755G>A		intron	N/A	ENSP00000347240.4
	LIMS2	ENST00000409455.5	TSL:1	c.-4-6755G>A		intron	N/A	ENSP00000386383.1

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151746 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000323 AC: 1 AN: 3100 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00196

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000611 AC: 66 AN: 1080932 Hom.: 0 Cov.: 31 AF XY: 0.0000623 AC XY: 32 AN XY: 513496

African (AFR) AF: 0.000848 AC: 19 AN: 22400

American (AMR) AF: 0.00 AC: 0 AN: 8602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14108

East Asian (EAS) AF: 0.00 AC: 0 AN: 25634

South Asian (SAS) AF: 0.00 AC: 0 AN: 21926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2880

European-Non Finnish (NFE) AF: 0.0000500 AC: 46 AN: 920920

Other (OTH) AF: 0.0000232 AC: 1 AN: 43052

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151854 Hom.: 0 Cov.: 32 AF XY: 0.000216 AC XY: 16 AN XY: 74230

African (AFR) AF: 0.000698 AC: 29 AN: 41532

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67828

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000196

Asia WGS AF: 0.000292 AC: 1 AN: 3434

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2W (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.2
DANN	Benign	0.91
PhyloP100		-1.2
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism

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: rs529824211; hg19: chr2-128421891;