15-34788322-T-C

Position:

• chr15-34788322-T-C

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+10891T>C 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 0.469 in 151,906 control chromosomes in the GnomAD database, including 18,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (18761 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: GJD2-DT NR_120329.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0510

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 15-34788322-T-C is Benign according to our data. Variant chr15-34788322-T-C is described in ClinVar as [Benign]. Clinvar id is 315647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJD2-DT	NR_120329.1	n.299+10891T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJD2-DT	ENST00000671663.1	n.95-22174T>C		intron_variant, non_coding_transcript_variant
GJD2-DT	ENST00000503496.6	n.299+10891T>C		intron_variant, non_coding_transcript_variant		2
GJD2-DT	ENST00000558707.3	n.280-1485T>C		intron_variant, non_coding_transcript_variant		3
GJD2-DT	ENST00000693120.2	n.117-1485T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71199 AN: 151788 Hom.: 18768 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.495

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: 0.469 AC: 71214 AN: 151906 Hom.: 18761 Cov.: 31 AF XY: 0.471 AC XY: 34938 AN XY: 74226

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.494

Alfa AF: 0.531 Hom.: 4599

Bravo AF: 0.454

Asia WGS AF: 0.425 AC: 1477 AN: 3474

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	-0.87
CADD	Benign	2.8
DANN	Benign	0.69

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: rs604689; hg19: chr15-35080523;