10-86699239-TTCTCTCTCTCTCTCTCTCTC-TTCTCTCTCTCTCTCTCTC

Variant names:

• chr10-86699239-TTC-T
• rs71019410
• NM_007078.3:c.896+6696_896+6697delCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_007078.3(LDB3):​c.896+6696_896+6697delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6405 hom., cov: 0)
  • Exomes 𝑓: 0.31 (3306 hom.)
  • Failed GnomAD Quality Control
• Consequence: LDB3 NM_007078.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.0920
• Publications: 5 publications found

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):

• 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

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-86699239-TTC-T is Benign according to our data. Variant chr10-86699239-TTC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007078.3. 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_007078.3	MANE Select	c.896+6696_896+6697delCT		intron	N/A	NP_009009.1	O75112-1
	LDB3	NM_001368067.1	MANE Plus Clinical	c.756-11_756-10delCT		intron	N/A	NP_001354996.1	A0A0S2Z530
	LDB3	NM_001171610.2		c.1100+6696_1100+6697delCT		intron	N/A	NP_001165081.1	O75112-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDB3	ENST00000361373.9	TSL:1 MANE Select	c.896+6669_896+6670delTC		intron	N/A	ENSP00000355296.3	O75112-1
	LDB3	ENST00000263066.11	TSL:1 MANE Plus Clinical	c.756-38_756-37delTC		intron	N/A	ENSP00000263066.7	O75112-6
	ENSG00000289258	ENST00000443292.2	TSL:1	c.2406-38_2406-37delTC		intron	N/A	ENSP00000393132.2	C9JWU6

Frequencies

GnomAD3 genomes AF: 0.288 AC: 42793 AN: 148394 Hom.: 6404 Cov.: 0

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.314 AC: 70850 AN: 225518 AF XY: 0.316

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.324

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.310 AC: 425276 AN: 1370514 Hom.: 3306 AF XY: 0.310 AC XY: 211978 AN XY: 683630

African (AFR) AF: 0.145 AC: 4626 AN: 31924

American (AMR) AF: 0.326 AC: 13978 AN: 42814

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8303 AN: 24744

East Asian (EAS) AF: 0.163 AC: 6237 AN: 38230

South Asian (SAS) AF: 0.277 AC: 22637 AN: 81616

European-Finnish (FIN) AF: 0.285 AC: 14350 AN: 50304

Middle Eastern (MID) AF: 0.326 AC: 1789 AN: 5496

European-Non Finnish (NFE) AF: 0.324 AC: 336436 AN: 1038504

Other (OTH) AF: 0.297 AC: 16920 AN: 56882

GnomAD4 genome AF: 0.288 AC: 42803 AN: 148504 Hom.: 6405 Cov.: 0 AF XY: 0.287 AC XY: 20719 AN XY: 72274

African (AFR) AF: 0.173 AC: 6975 AN: 40428

American (AMR) AF: 0.378 AC: 5646 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1285 AN: 3434

East Asian (EAS) AF: 0.203 AC: 1014 AN: 5004

South Asian (SAS) AF: 0.223 AC: 1024 AN: 4586

European-Finnish (FIN) AF: 0.284 AC: 2850 AN: 10028

Middle Eastern (MID) AF: 0.382 AC: 110 AN: 288

European-Non Finnish (NFE) AF: 0.343 AC: 22926 AN: 66864

Other (OTH) AF: 0.305 AC: 626 AN: 2050

Alfa AF: 0.262 Hom.: 224

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

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: rs71019410; hg19: chr10-88458996; COSMIC: COSV53938110;