4-16595821-A-G

Variant names:

• chr4-16595821-A-G
• rs1004836816
• NM_001290.5:c.290T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001290.5(LDB2):​c.290T>C​(p.Val97Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LDB2 NM_001290.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93
• Publications: 1 publications found

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]

ENSG00000248138 (HGNC:58741):

LOC124900604 (HGNC:):

ACMG classification

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, 0.748

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	NM_001290.5	MANE Select	c.290T>C	p.Val97Ala	missense	Exon 3 of 8	NP_001281.1	O43679-1
	LDB2	NM_001304434.2		c.290T>C	p.Val97Ala	missense	Exon 3 of 8	NP_001291363.1	G5E9Y7
	LDB2	NM_001130834.3		c.290T>C	p.Val97Ala	missense	Exon 3 of 9	NP_001124306.1	O43679-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB2	ENST00000304523.10	TSL:1 MANE Select	c.290T>C	p.Val97Ala	missense	Exon 3 of 8	ENSP00000306772.5	O43679-1
	LDB2	ENST00000441778.6	TSL:1	c.290T>C	p.Val97Ala	missense	Exon 3 of 9	ENSP00000392089.2	O43679-2
	LDB2	ENST00000502640.5	TSL:1	c.290T>C	p.Val97Ala	missense	Exon 3 of 8	ENSP00000423963.1	E9PFI4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0068	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.53
Sift	Benign	0.31	T
Sift4G	Benign	0.18	T
Polyphen		0.14	B
Vest4		0.57
MutPred		0.51		Loss of sheet (P = 0.0181)
MVP		0.51
MPC		1.2
ClinPred		0.92	D
GERP RS		5.6
PromoterAI		0.016	Neutral
Varity_R		0.25
gMVP		0.94
Mutation Taster		=143/157	disease causing

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: rs1004836816; hg19: chr4-16597444;