rs981648501

Variant names:

• chr15-34788612-G-A
• rs981648501
• ENST00000503496.6:n.299+11181G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000503496.6(GJD2-DT):​n.299+11181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 151,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GJD2-DT ENST00000503496.6 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.124
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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+11181G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJD2-DT	ENST00000503496.6	TSL:2	n.299+11181G>A		intron	N/A
	GJD2-DT	ENST00000558707.4	TSL:3	n.322-1195G>A		intron	N/A
	GJD2-DT	ENST00000671663.2		n.139-21884G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000278 AC: 42 AN: 151054 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00839

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000484

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 44 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

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) AF: 0.00 AC: 0 AN: 2

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 18

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.000278 AC: 42 AN: 151054 Hom.: 0 Cov.: 31 AF XY: 0.000271 AC XY: 20 AN XY: 73720

African (AFR) AF: 0.00 AC: 0 AN: 41052

American (AMR) AF: 0.0000662 AC: 1 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00839 AC: 29 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67792

Other (OTH) AF: 0.000484 AC: 1 AN: 2066

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.000355

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated cardiomyopathy 1R (1)
-	1	-	Hypertrophic cardiomyopathy 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.40
PhyloP100		-0.12

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: rs981648501; hg19: chr15-35080813;