rs2658509

Positions:

• chr4-16725163-A-C
• chr4-16725163-A-G
• chr4-16725163-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290.5(LDB2):​c.235+33995T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,912 control chromosomes in the GnomAD database, including 17,549 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 0.47 (17549 hom., cov: 31)
• Consequence: LDB2 NM_001290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

Genes affected

LDB2 (HGNC:6533): (LIM domain binding 2) The protein encoded by this gene belongs to the LIM-domain binding family. Members of this family are characterized by a conserved nuclear localization sequence, an amino-terminal homodimerization domain and a carboxy-terminal LIM interaction domain. These proteins function as adapter molecules to allow assembly of transcriptional regulatory complexes. Genetic association studies suggest functions for this gene in rhegmatogenous retinal detachment and coronary artery disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

LDB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDB2	NM_001290.5	c.235+33995T>G		intron_variant		ENST00000304523.10	NP_001281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDB2	ENST00000304523.10	c.235+33995T>G		intron_variant		1	NM_001290.5	ENSP00000306772.5

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71897 AN: 151794 Hom.: 17526 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.474 AC: 71964 AN: 151912 Hom.: 17549 Cov.: 31 AF XY: 0.481 AC XY: 35721 AN XY: 74230

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.459

Alfa AF: 0.464 Hom.: 9318

Bravo AF: 0.472

Asia WGS AF: 0.609 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2658509; hg19: chr4-16726786;