NM_007204.5:c.1907T>G

Variant names:

• chr1-111766331-T-G
• rs197412
• NM_007204.5:c.1907T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007204.5(DDX20):​c.1907T>G​(p.Ile636Ser) 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. 15/21 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. I636T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX20 NM_007204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

Genes affected

DDX20 (HGNC:2743): (DEAD-box helicase 20) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0671756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX20	NM_007204.5	c.1907T>G	p.Ile636Ser	missense_variant	Exon 11 of 11	ENST00000369702.5	NP_009135.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX20	ENST00000369702.5	c.1907T>G	p.Ile636Ser	missense_variant	Exon 11 of 11	1	NM_007204.5	ENSP00000358716.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.84
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.81	N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.76	N;N
REVEL	Benign	0.077
Sift	Benign	0.34	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.0	B;B
Vest4		0.056
MutPred		0.21		Gain of disorder (P = 0.017);.;
MVP		0.40
MPC		0.12
ClinPred		0.075	T
GERP RS		3.9
Varity_R		0.023
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs197412; hg19: chr1-112308953;