chr5-118939200-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173666.4(DTWD2):c.400G>A(p.Glu134Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000874 in 1,601,960 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
DTWD2
NM_173666.4 missense
NM_173666.4 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 6.36
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15239424).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTWD2 | NM_173666.4 | c.400G>A | p.Glu134Lys | missense_variant | 3/6 | ENST00000510708.6 | |
DTWD2 | NM_001308081.2 | c.202G>A | p.Glu68Lys | missense_variant | 3/6 | ||
DTWD2 | XM_011543338.4 | c.400G>A | p.Glu134Lys | missense_variant | 3/7 | ||
DTWD2 | XM_011543340.3 | c.202G>A | p.Glu68Lys | missense_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTWD2 | ENST00000510708.6 | c.400G>A | p.Glu134Lys | missense_variant | 3/6 | 1 | NM_173666.4 | P1 | |
DTWD2 | ENST00000304058.8 | c.202G>A | p.Glu68Lys | missense_variant | 3/6 | 1 | |||
DTWD2 | ENST00000515439.7 | c.309+5359G>A | intron_variant | 5 | |||||
DTWD2 | ENST00000506980.2 | c.400G>A | p.Glu134Lys | missense_variant, NMD_transcript_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000412 AC: 10AN: 242704Hom.: 0 AF XY: 0.0000304 AC XY: 4AN XY: 131386
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GnomAD4 exome AF: 0.00000621 AC: 9AN: 1449688Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3AN XY: 721198
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74466
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.400G>A (p.E134K) alteration is located in exon 3 (coding exon 3) of the DTWD2 gene. This alteration results from a G to A substitution at nucleotide position 400, causing the glutamic acid (E) at amino acid position 134 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.065
.;B
Vest4
MutPred
0.43
.;Gain of MoRF binding (P = 0.0107);
MVP
MPC
0.046
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at