15-34789373-C-T

Variant names:

• chr15-34789373-C-T
• rs589759
• ENST00000503496.6:n.299+11942C>T

Variant summary

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

The ENST00000503496.6(GJD2-DT):​n.299+11942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 161,320 control chromosomes in the GnomAD database, including 40,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38413 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2138 hom.)
• Consequence: GJD2-DT ENST00000503496.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.706
• Publications: 7 publications found

Genes affected

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 15-34789373-C-T is Benign according to our data. Variant chr15-34789373-C-T is described in ClinVar as Benign. ClinVar VariationId is 315668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503496.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD2-DT	NR_120329.1		n.299+11942C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD2-DT	ENST00000503496.6	TSL:2	n.299+11942C>T		intron	N/A
	GJD2-DT	ENST00000558707.4	TSL:3	n.322-434C>T		intron	N/A
	GJD2-DT	ENST00000671663.2		n.139-21123C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107549 AN: 151950 Hom.: 38365 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.712

GnomAD4 exome AF: 0.670 AC: 6198 AN: 9252 Hom.: 2138 Cov.: 0 AF XY: 0.671 AC XY: 3273 AN XY: 4878

African (AFR) AF: 0.728 AC: 147 AN: 202

American (AMR) AF: 0.625 AC: 100 AN: 160

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 193 AN: 246

East Asian (EAS) AF: 0.421 AC: 528 AN: 1254

South Asian (SAS) AF: 0.750 AC: 63 AN: 84

European-Finnish (FIN) AF: 0.714 AC: 957 AN: 1340

Middle Eastern (MID) AF: 0.850 AC: 34 AN: 40

European-Non Finnish (NFE) AF: 0.704 AC: 3825 AN: 5432

Other (OTH) AF: 0.711 AC: 351 AN: 494

GnomAD4 genome AF: 0.708 AC: 107650 AN: 152068 Hom.: 38413 Cov.: 32 AF XY: 0.703 AC XY: 52233 AN XY: 74320

African (AFR) AF: 0.715 AC: 29641 AN: 41474

American (AMR) AF: 0.626 AC: 9563 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2785 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2519 AN: 5158

South Asian (SAS) AF: 0.737 AC: 3552 AN: 4818

European-Finnish (FIN) AF: 0.718 AC: 7579 AN: 10560

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49604 AN: 67984

Other (OTH) AF: 0.713 AC: 1506 AN: 2112

Alfa AF: 0.711 Hom.: 46353

Bravo AF: 0.695

Asia WGS AF: 0.647 AC: 2250 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated cardiomyopathy 1R (1)
-	-	1	Hypertrophic cardiomyopathy 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.71
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: rs589759; hg19: chr15-35081574;