Genetic Variant LDB2:p.Gly96Trp (chr4-16595825-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6

The NM_001290.5(LDB2):c.286G>T(p.Gly96Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

LDB2
NM_001290.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.57

Publications

0 publications found

Variant links:

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 links:

ENSG00000248138 (HGNC:58741):

ENSG00000248138 links:

LOC124900604 (HGNC:):

LOC124900604 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

BP6

Variant 4-16595825-C-A is Benign according to our data. Variant chr4-16595825-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2681371.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDB2	NM_001290.5	MANE Select	c.286G>T	p.Gly96Trp	missense	Exon 3 of 8	NP_001281.1	O43679-1
LDB2	NM_001304434.2		c.286G>T	p.Gly96Trp	missense	Exon 3 of 8	NP_001291363.1	G5E9Y7
LDB2	NM_001130834.3		c.286G>T	p.Gly96Trp	missense	Exon 3 of 9	NP_001124306.1	O43679-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDB2	ENST00000304523.10	TSL:1 MANE Select	c.286G>T	p.Gly96Trp	missense	Exon 3 of 8	ENSP00000306772.5	O43679-1
LDB2	ENST00000441778.6	TSL:1	c.286G>T	p.Gly96Trp	missense	Exon 3 of 9	ENSP00000392089.2	O43679-2
LDB2	ENST00000502640.5	TSL:1	c.286G>T	p.Gly96Trp	missense	Exon 3 of 8	ENSP00000423963.1	E9PFI4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.93

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.0

PhyloP100

7.6

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-7.6

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MutPred

0.79

Gain of glycosylation at Y101 (P = 0.0346)

MVP

0.40

MPC

1.9

ClinPred

1.0

GERP RS

5.6

PromoterAI

-0.052

Neutral

(source)

Varity_R

0.91

gMVP

0.95

Mutation Taster

=104/196

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over