15-34789373-C-T

Position:

• chr15-34789373-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+11942C>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 0.706 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 NR_120329.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.706

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=-0.71).
• BP6: Variant 15-34789373-C-T is Benign according to our data. Variant chr15-34789373-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJD2-DT	NR_120329.1	n.299+11942C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJD2-DT	ENST00000671663.1	n.95-21123C>T		intron_variant, non_coding_transcript_variant
GJD2-DT	ENST00000503496.6	n.299+11942C>T		intron_variant, non_coding_transcript_variant		2
GJD2-DT	ENST00000558707.3	n.280-434C>T		intron_variant, non_coding_transcript_variant		3
GJD2-DT	ENST00000693120.2	n.117-434C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.728

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.785

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.711

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

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.713

Alfa AF: 0.714 Hom.: 35214

Bravo AF: 0.695

Asia WGS AF: 0.647 AC: 2250 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 13, 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 13, 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

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.7
DANN	Benign	0.70

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: rs589759; hg19: chr15-35081574;