19-42215187-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133328.4(DEDD2):​c.394C>A​(p.Arg132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R132C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEDD2 NM_133328.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13807449).

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>A	p.Arg132Ser	missense	Exon 3 of 5	NP_579874.1	Q8WXF8-1
	DEDD2	NM_001270614.2		c.394C>A	p.Arg132Ser	missense	Exon 3 of 5	NP_001257543.1	Q8WXF8-1
	DEDD2	NM_001270615.2		c.394C>A	p.Arg132Ser	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>A	p.Arg132Ser	missense	Exon 3 of 5	ENSP00000471512.1	Q8WXF8-1
	DEDD2	ENST00000336034.8	TSL:1	c.394C>A	p.Arg132Ser	missense	Exon 3 of 5	ENSP00000336972.4	Q8WXF8-2
	DEDD2	ENST00000598727.5	TSL:1	c.394C>A	p.Arg132Ser	missense	Exon 3 of 5	ENSP00000469233.1	M0QXK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.21
Sift	Benign	0.75	T
Sift4G	Benign	0.77	T
Polyphen		0.87	P
Vest4		0.30
MutPred		0.28		Gain of phosphorylation at R132 (P = 2e-04)
MVP		0.42
MPC		0.76
ClinPred		0.64	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.44
Mutation Taster		=93/7	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;