rs8037241

Positions:

• chr15-34788967-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_120329.1(GJD2-DT):​n.299+11536G>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 0.21 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 NR_120329.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.317

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -14 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 id is 315659.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
GJD2-DT	NR_120329.1	n.299+11536G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJD2-DT	ENST00000671663.1	n.95-21529G>C		intron_variant, non_coding_transcript_variant
GJD2-DT	ENST00000503496.6	n.299+11536G>C		intron_variant, non_coding_transcript_variant		2
GJD2-DT	ENST00000558707.3	n.280-840G>C		intron_variant, non_coding_transcript_variant		3
GJD2-DT	ENST00000693120.2	n.117-840G>C		intron_variant, non_coding_transcript_variant

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

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.210

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:2

Revision: criteria provided, single submitter

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.67

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: rs8037241; hg19: chr15-35081168;