rs1344111303

Variant names:

• chr19-42199739-C-T
• rs1344111303
• NM_133328.4:c.680G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-42199739-C-T
• chr19-42199739-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_133328.4(DEDD2):​c.680G>A​(p.Arg227Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DEDD2 NM_133328.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• Publications: 0 publications found

Genes affected

DEDD2 (HGNC:24450): (death effector domain containing 2) This gene encodes a nuclear-localized protein containing a death effector domain (DED). The encoded protein may regulate the trafficking of caspases and other proteins into the nucleus during death receptor-induced apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133328.4. 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
	DEDD2	NM_133328.4	MANE Select	c.680G>A	p.Arg227Gln	missense	Exon 5 of 5	NP_579874.1	Q8WXF8-1
	DEDD2	NM_001270614.2		c.680G>A	p.Arg227Gln	missense	Exon 5 of 5	NP_001257543.1	Q8WXF8-1
	DEDD2	NM_001270615.2		c.665G>A	p.Arg222Gln	missense	Exon 5 of 5	NP_001257544.1	Q8WXF8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEDD2	ENST00000596251.6	TSL:1 MANE Select	c.680G>A	p.Arg227Gln	missense	Exon 5 of 5	ENSP00000471512.1	Q8WXF8-1
	DEDD2	ENST00000336034.8	TSL:1	c.665G>A	p.Arg222Gln	missense	Exon 5 of 5	ENSP00000336972.4	Q8WXF8-2
	DEDD2	ENST00000595337.5	TSL:3	c.680G>A	p.Arg227Gln	missense	Exon 5 of 5	ENSP00000470082.1	Q8WXF8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461034 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726840

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111628

Other (OTH) AF: 0.0000166 AC: 1 AN: 60310

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.1
PrimateAI	Uncertain	0.75	T
REVEL	Benign	0.15
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.60
MutPred		0.38		Loss of MoRF binding (P = 0.0397)
MVP		0.65
MPC		0.96
ClinPred		0.93	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.27
gMVP		0.79
Mutation Taster		=87/13	polymorphism

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: rs1344111303; hg19: chr19-42703891;