15-34790024-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_120329.1(GJD2-DT):n.299+12593C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 234,434 control chromosomes in the GnomAD database, including 8,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5236 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2989 hom.)
• Consequence: GJD2-DT NR_120329.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.284

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 15-34790024-C-T is Benign according to our data. Variant chr15-34790024-C-T is described in ClinVar as [Benign]. Clinvar id is 315694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJD2-DT	NR_120329.1	n.299+12593C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJD2-DT	ENST00000671663.1	n.95-20472C>T		intron_variant, non_coding_transcript_variant
GJD2-DT	ENST00000558707.3	n.497C>T		non_coding_transcript_exon_variant	3/3	3
GJD2-DT	ENST00000693120.2	n.334C>T		non_coding_transcript_exon_variant	2/2
GJD2-DT	ENST00000503496.6	n.299+12593C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38843 AN: 151992 Hom.: 5233 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.262 AC: 21536 AN: 82324 Hom.: 2989 Cov.: 0 AF XY: 0.266 AC XY: 11320 AN XY: 42608

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.255 AC: 38854 AN: 152110 Hom.: 5236 Cov.: 32 AF XY: 0.257 AC XY: 19110 AN XY: 74372

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.266

Alfa AF: 0.263 Hom.: 6964

Bravo AF: 0.258

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dilated cardiomyopathy 1R Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypertrophic cardiomyopathy 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.1
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs1370154; hg19: chr15-35082225;