15-34788738-G-A

Variant names:

• chr15-34788738-G-A
• rs112660730
• ENST00000503496.6:n.299+11307G>A

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+11307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 152,260 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (177 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GJD2-DT ENST00000503496.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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=-0.9).
• BP6: Variant 15-34788738-G-A is Benign according to our data. Variant chr15-34788738-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 315654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJD2-DT	NR_120329.1	n.299+11307G>A		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+11307G>A		intron_variant	Intron 2 of 2	2
GJD2-DT	ENST00000558707.3	n.280-1069G>A		intron_variant	Intron 2 of 2	3
GJD2-DT	ENST00000671663.1	n.95-21758G>A		intron_variant	Intron 1 of 1
GJD2-DT	ENST00000693120.2	n.117-1069G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6375 AN: 152142 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0614

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0526

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: 0.0418 AC: 6372 AN: 152260 Hom.: 177 Cov.: 32 AF XY: 0.0406 AC XY: 3025 AN XY: 74452

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0614

Gnomad4 NFE AF: 0.0630

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0538 Hom.: 57

Bravo AF: 0.0396

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dilated cardiomyopathy 1R Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Hypertrophic cardiomyopathy 11 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.56

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: rs112660730; hg19: chr15-35080939;