19-42215187-G-A

Variant names:

• chr19-42215187-G-A
• rs376679587
• NM_133328.4:c.394C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_133328.4(DEDD2):​c.394C>T​(p.Arg132Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: DEDD2 NM_133328.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• 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]

ENSG00000288671 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.24131453).

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.394C>T	p.Arg132Cys	missense	Exon 3 of 5	NP_579874.1	Q8WXF8-1
	DEDD2	NM_001270614.2		c.394C>T	p.Arg132Cys	missense	Exon 3 of 5	NP_001257543.1	Q8WXF8-1
	DEDD2	NM_001270615.2		c.394C>T	p.Arg132Cys	missense	Exon 3 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.394C>T	p.Arg132Cys	missense	Exon 3 of 5	ENSP00000471512.1	Q8WXF8-1
	DEDD2	ENST00000336034.8	TSL:1	c.394C>T	p.Arg132Cys	missense	Exon 3 of 5	ENSP00000336972.4	Q8WXF8-2
	DEDD2	ENST00000598727.5	TSL:1	c.394C>T	p.Arg132Cys	missense	Exon 3 of 5	ENSP00000469233.1	M0QXK7

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461550 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727056

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

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

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111912

Other (OTH) AF: 0.0000331 AC: 2 AN: 60372

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.000327 AC: 5 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.25
Sift	Benign	0.098	T
Sift4G	Uncertain	0.057	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.30		Gain of sheet (P = 0.0221)
MVP		0.55
MPC		0.99
ClinPred		0.75	D
GERP RS		3.7
Varity_R		0.12
gMVP		0.45
Mutation Taster		=91/9	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: rs376679587; hg19: chr19-42719339;