15-34788730-T-C

Variant names:

• chr15-34788730-T-C
• rs533021
• ENST00000503496.6:n.299+11299T>C

Variant summary

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

The ENST00000503496.6(GJD2-DT):​n.299+11299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,060 control chromosomes in the GnomAD database, including 24,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24431 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GJD2-DT ENST00000503496.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.167

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=-0.87).
• BP6: Variant 15-34788730-T-C is Benign according to our data. Variant chr15-34788730-T-C is described in ClinVar as [Benign]. Clinvar id is 315653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJD2-DT	NR_120329.1	n.299+11299T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJD2-DT	ENST00000503496.6	n.299+11299T>C		intron_variant	Intron 2 of 2	2
GJD2-DT	ENST00000558707.3	n.280-1077T>C		intron_variant	Intron 2 of 2	3
GJD2-DT	ENST00000671663.1	n.95-21766T>C		intron_variant	Intron 1 of 1
GJD2-DT	ENST00000693120.2	n.117-1077T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83756 AN: 151942 Hom.: 24430 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.566

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.551 AC: 83785 AN: 152060 Hom.: 24431 Cov.: 32 AF XY: 0.551 AC XY: 40919 AN XY: 74318

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.564

Alfa AF: 0.613 Hom.: 23165

Bravo AF: 0.527

Asia WGS AF: 0.437 AC: 1523 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1R Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.68

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: rs533021; hg19: chr15-35080931;