15-34788322-T-C

Variant names:

• chr15-34788322-T-C
• rs604689
• ENST00000503496.6:n.299+10891T>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+10891T>C variant causes a intron 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 ENST00000503496.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0510
• 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=-0.87).
• BP6: Variant 15-34788322-T-C is Benign according to our data. Variant chr15-34788322-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503496.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD2-DT	NR_120329.1		n.299+10891T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD2-DT	ENST00000503496.6	TSL:2	n.299+10891T>C		intron	N/A
	GJD2-DT	ENST00000558707.4	TSL:3	n.322-1485T>C		intron	N/A
	GJD2-DT	ENST00000671663.2		n.139-22174T>C		intron	N/A

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

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

African (AFR) AF: 0.211 AC: 8734 AN: 41446

American (AMR) AF: 0.568 AC: 8677 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1716 AN: 5148

South Asian (SAS) AF: 0.475 AC: 2286 AN: 4810

European-Finnish (FIN) AF: 0.589 AC: 6188 AN: 10508

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39841 AN: 67944

Other (OTH) AF: 0.494 AC: 1038 AN: 2102

Alfa AF: 0.444 Hom.: 5224

Bravo AF: 0.454

Asia WGS AF: 0.425 AC: 1477 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated cardiomyopathy 1R (1)
-	-	1	Hypertrophic cardiomyopathy 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		0.051
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: rs604689; hg19: chr15-35080523;