ENST00000503496.6:n.299+11536G>C

Variant names:

• chr15-34788967-G-C
• rs8037241
• ENST00000503496.6:n.299+11536G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000503496.6(GJD2-DT):​n.299+11536G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,172 control chromosomes in the GnomAD database, including 3,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3384 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GJD2-DT ENST00000503496.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.317
• Publications: 5 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-34788967-G-C is Benign according to our data. Variant chr15-34788967-G-C is described in ClinVar as Benign. ClinVar VariationId is 315659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJD2-DT	NR_120329.1	n.299+11536G>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+11536G>C		intron_variant	Intron 2 of 2	2
GJD2-DT	ENST00000558707.4	n.322-840G>C		intron_variant	Intron 2 of 2	3
GJD2-DT	ENST00000671663.2	n.139-21529G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31973 AN: 152054 Hom.: 3376 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.211

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.210 AC: 32012 AN: 152172 Hom.: 3384 Cov.: 32 AF XY: 0.210 AC XY: 15601 AN XY: 74392

African (AFR) AF: 0.244 AC: 10131 AN: 41524

American (AMR) AF: 0.214 AC: 3264 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3470

East Asian (EAS) AF: 0.155 AC: 801 AN: 5180

South Asian (SAS) AF: 0.226 AC: 1087 AN: 4816

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10586

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13572 AN: 67996

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.203 Hom.: 410

Bravo AF: 0.215

Asia WGS AF: 0.211 AC: 731 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8037241; hg19: chr15-35081168;