rs2803555

Variant names:

• chr10-86668401-T-C
• rs2803555
• ENST00000443292.2:c.1487-268T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-86668401-T-C
• chr10-86668401-T-A
• chr10-86668401-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001368064.1(LDB3):​c.-23-268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 503,232 control chromosomes in the GnomAD database, including 144,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48097 hom., cov: 34)
  • Exomes 𝑓: 0.74 (96429 hom.)
• Consequence: LDB3 NM_001368064.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.148
• Publications: 8 publications found

Genes affected

ENSG00000289258 (HGNC:):

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):

• dilated cardiomyopathy

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: ClinGen
• myofibrillar myopathy 4

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 10-86668401-T-C is Benign according to our data. Variant chr10-86668401-T-C is described in ClinVar as Benign. ClinVar VariationId is 671123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368064.1. 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
	LDB3	NM_001368064.1		c.-23-268T>C		intron	N/A	NP_001354993.1	V5T7C5
	LDB3	NM_001368063.1		c.-23-268T>C		intron	N/A	NP_001354992.1	A0A0S2Z501
	LDB3	NM_001368068.1		c.-23-268T>C		intron	N/A	NP_001354997.1	A0A0S2Z530

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289258	ENST00000443292.2	TSL:1	c.1487-268T>C		intron	N/A	ENSP00000393132.2	C9JWU6
	LDB3	ENST00000871445.1		c.-193T>C		5_prime_UTR	Exon 1 of 13	ENSP00000541504.1
	LDB3	ENST00000871441.1		c.-23-268T>C		intron	N/A	ENSP00000541500.1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119786 AN: 152110 Hom.: 48028 Cov.: 34

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.738 AC: 259110 AN: 351004 Hom.: 96429 Cov.: 0 AF XY: 0.741 AC XY: 137604 AN XY: 185812

African (AFR) AF: 0.942 AC: 9964 AN: 10578

American (AMR) AF: 0.781 AC: 14466 AN: 18532

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 8051 AN: 10806

East Asian (EAS) AF: 0.819 AC: 17668 AN: 21582

South Asian (SAS) AF: 0.793 AC: 36205 AN: 45638

European-Finnish (FIN) AF: 0.732 AC: 14509 AN: 19822

Middle Eastern (MID) AF: 0.757 AC: 1094 AN: 1446

European-Non Finnish (NFE) AF: 0.702 AC: 142527 AN: 202910

Other (OTH) AF: 0.743 AC: 14626 AN: 19690

GnomAD4 genome AF: 0.788 AC: 119914 AN: 152228 Hom.: 48097 Cov.: 34 AF XY: 0.791 AC XY: 58865 AN XY: 74430

African (AFR) AF: 0.946 AC: 39309 AN: 41566

American (AMR) AF: 0.773 AC: 11833 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2615 AN: 3468

East Asian (EAS) AF: 0.802 AC: 4146 AN: 5168

South Asian (SAS) AF: 0.804 AC: 3879 AN: 4826

European-Finnish (FIN) AF: 0.730 AC: 7738 AN: 10596

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47784 AN: 67974

Other (OTH) AF: 0.762 AC: 1610 AN: 2114

Alfa AF: 0.755 Hom.: 5964

Bravo AF: 0.795

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		0.15
PromoterAI		-0.14	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2803555; hg19: chr10-88428158;