GeneBe

rs71019410

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_007078.3(LDB3):​c.896+6678_896+6697delCTCTCTCTCTCTCTCTCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,384 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LDB3
NM_007078.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

Publications

0 publications found
Variant links:
Genes affected
LDB3 (HGNC:15710): (LIM domain binding 3) This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]
LDB3 Gene-Disease associations (from GenCC):
  • myofibrillar myopathy 4
    Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • dilated cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • familial dilated cardiomyopathy
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6
Variant 10-86699239-TTCTCTCTCTCTCTCTCTCTC-T is Benign according to our data. Variant chr10-86699239-TTCTCTCTCTCTCTCTCTCTC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2854959.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LDB3NM_007078.3 linkc.896+6678_896+6697delCTCTCTCTCTCTCTCTCTCT intron_variant Intron 7 of 13 ENST00000361373.9 NP_009009.1 O75112-1
LDB3NM_001368067.1 linkc.756-29_756-10delCTCTCTCTCTCTCTCTCTCT intron_variant Intron 8 of 8 ENST00000263066.11 NP_001354996.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LDB3ENST00000361373.9 linkc.896+6669_896+6688delTCTCTCTCTCTCTCTCTCTC intron_variant Intron 7 of 13 1 NM_007078.3 ENSP00000355296.3 O75112-1
LDB3ENST00000263066.11 linkc.756-38_756-19delTCTCTCTCTCTCTCTCTCTC intron_variant Intron 8 of 8 1 NM_001368067.1 ENSP00000263066.7 O75112-6
ENSG00000289258ENST00000443292.2 linkc.2406-38_2406-19delTCTCTCTCTCTCTCTCTCTC intron_variant Intron 17 of 17 1 ENSP00000393132.2 C9JWU6

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
7.07e-7
AC:
1
AN:
1414384
Hom.:
0
AF XY:
0.00000142
AC XY:
1
AN XY:
705990
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32414
American (AMR)
AF:
0.00
AC:
0
AN:
44422
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25656
East Asian (EAS)
AF:
0.0000256
AC:
1
AN:
39012
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85052
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51964
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5666
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1071552
Other (OTH)
AF:
0.00
AC:
0
AN:
58646
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Myofibrillar myopathy 4 Benign:1
Apr 18, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs71019410; hg19: chr10-88458996; API