dbSNP rs604689: GJD2-DT:n.299+10891T>C (chr15-34788322-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0510

Publications

5 publications found

Variant links:

Genes affected

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

GJD2-DT links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000503496.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

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

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
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.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.469

AC:

71214

AN:

151906

Hom.:

18761

Cov.:

AF XY:

0.471

AC XY:

34938

AN XY:

74226

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1752

3504

5257

7009

8761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.444

Hom.:

5224

Bravo

AF:

0.454

Asia WGS

AF:

0.425

AC:

1477

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dilated cardiomyopathy 1R (1)

Hypertrophic cardiomyopathy 11 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.8

(source)

DANN

Benign

0.69

PhyloP100

0.051

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over