11-30899619-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001387274.1(DCDC1):​c.4687G>A​(p.Glu1563Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,567,600 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 9 hom., cov: 32)
Exomes 𝑓: 0.011 ( 85 hom. )

Consequence

DCDC1
NM_001387274.1 missense

Scores

14

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.169
Variant links:
Genes affected
DCDC1 (HGNC:20625): (doublecortin domain containing 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene is a hydrophilic, intracellular protein. It contains a single doublecortin domain and is unable to bind microtubules and to regulate microtubule polymerization. This gene is mainly expressed in adult testis. It does not have a mouse homolog. [provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0050623417).
BP6
Variant 11-30899619-C-T is Benign according to our data. Variant chr11-30899619-C-T is described in ClinVar as [Benign]. Clinvar id is 2641698.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCDC1NM_001387274.1 linkc.4687G>A p.Glu1563Lys missense_variant Exon 34 of 39 ENST00000684477.1 NP_001374203.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCDC1ENST00000684477.1 linkc.4687G>A p.Glu1563Lys missense_variant Exon 34 of 39 NM_001387274.1 ENSP00000507427.1 A0A804HJA9

Frequencies

GnomAD3 genomes
AF:
0.00853
AC:
1297
AN:
152004
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00246
Gnomad AMI
AF:
0.0186
Gnomad AMR
AF:
0.00925
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00538
Gnomad FIN
AF:
0.0111
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.0126
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00752
AC:
1499
AN:
199286
Hom.:
4
AF XY:
0.00795
AC XY:
850
AN XY:
106860
show subpopulations
Gnomad AFR exome
AF:
0.00152
Gnomad AMR exome
AF:
0.00379
Gnomad ASJ exome
AF:
0.00160
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00440
Gnomad FIN exome
AF:
0.00942
Gnomad NFE exome
AF:
0.0118
Gnomad OTH exome
AF:
0.0113
GnomAD4 exome
AF:
0.0109
AC:
15446
AN:
1415478
Hom.:
85
Cov.:
30
AF XY:
0.0109
AC XY:
7653
AN XY:
701212
show subpopulations
Gnomad4 AFR exome
AF:
0.00202
Gnomad4 AMR exome
AF:
0.00456
Gnomad4 ASJ exome
AF:
0.00216
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00455
Gnomad4 FIN exome
AF:
0.0109
Gnomad4 NFE exome
AF:
0.0125
Gnomad4 OTH exome
AF:
0.00920
GnomAD4 genome
AF:
0.00853
AC:
1297
AN:
152122
Hom.:
9
Cov.:
32
AF XY:
0.00828
AC XY:
616
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00246
Gnomad4 AMR
AF:
0.00924
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00539
Gnomad4 FIN
AF:
0.0111
Gnomad4 NFE
AF:
0.0126
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.0109
Hom.:
21
Bravo
AF:
0.00766
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.0133
AC:
114
ExAC
AF:
0.00686
AC:
829
Asia WGS
AF:
0.00318
AC:
11
AN:
3472

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DCDC5-related condition Benign:1
May 15, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Oct 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

DCDC1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
3.4
DANN
Benign
0.89
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.041
N
LIST_S2
Benign
0.67
T;T
MetaRNN
Benign
0.0051
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.33
T
REVEL
Benign
0.0050
Sift4G
Benign
0.61
T;T
Vest4
0.12
MVP
0.34
ClinPred
0.0076
T
GERP RS
1.6
gMVP
0.11

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117396197; hg19: chr11-30921166; COSMIC: COSV100337794; API