NM_001099434.2:c.126G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001099434.2(DCDC2B):​c.126G>C​(p.Glu42Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E42K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DCDC2B
NM_001099434.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.581
Variant links:
Genes affected
DCDC2B (HGNC:32576): (doublecortin domain containing 2B) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. [provided by RefSeq, Sep 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30102694).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCDC2BNM_001099434.2 linkc.126G>C p.Glu42Asp missense_variant Exon 1 of 9 ENST00000409358.2 NP_001092904.1 A2VCK2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCDC2BENST00000409358.2 linkc.126G>C p.Glu42Asp missense_variant Exon 1 of 9 1 NM_001099434.2 ENSP00000386870.1 A2VCK2
DCDC2BENST00000487056.1 linkn.124G>C non_coding_transcript_exon_variant Exon 1 of 7 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461690
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.126G>C (p.E42D) alteration is located in exon 1 (coding exon 1) of the DCDC2B gene. This alteration results from a G to C substitution at nucleotide position 126, causing the glutamic acid (E) at amino acid position 42 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.34
Sift
Benign
0.14
T
Sift4G
Benign
0.079
T
Polyphen
0.54
P
Vest4
0.33
MutPred
0.54
Loss of helix (P = 0.1299);
MVP
0.74
MPC
0.13
ClinPred
0.77
D
GERP RS
0.91
Varity_R
0.14
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-32674820; API