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6-24174739-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_016356.5(DCDC2):c.1422C>T(p.Ala474=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000919 in 1,610,590 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

DCDC2
NM_016356.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.27
Variant links:
Genes affected
DCDC2 (HGNC:18141): (doublecortin domain containing 2) This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-24174739-G-A is Benign according to our data. Variant chr6-24174739-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1195693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.27 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DCDC2NM_016356.5 linkuse as main transcriptc.1422C>T p.Ala474= synonymous_variant 10/10 ENST00000378454.8
DCDC2NM_001195610.2 linkuse as main transcriptc.1422C>T p.Ala474= synonymous_variant 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DCDC2ENST00000378454.8 linkuse as main transcriptc.1422C>T p.Ala474= synonymous_variant 10/101 NM_016356.5 P1Q9UHG0-1
DCDC2ENST00000378450.6 linkuse as main transcriptc.681C>T p.Ala227= synonymous_variant 3/31 Q9UHG0-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000922
AC:
14
AN:
151890
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000194
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000876
AC:
22
AN:
251136
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000919
AC:
134
AN:
1458700
Hom.:
0
Cov.:
31
AF XY:
0.0000909
AC XY:
66
AN XY:
725898
show subpopulations
Gnomad4 AFR exome
AF:
0.0000899
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.0000768
Gnomad4 EAS exome
AF:
0.0000757
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000105
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000922
AC:
14
AN:
151890
Hom.:
0
Cov.:
32
AF XY:
0.0000944
AC XY:
7
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.000194
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000164
Hom.:
0
Bravo
AF:
0.0000831
Asia WGS
AF:
0.000289
AC:
1
AN:
3474

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 66;C4479344:Isolated neonatal sclerosing cholangitis Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 19, 2023- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJan 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.16
Dann
Benign
0.34

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

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

Other links and lift over

dbSNP: rs146868469; hg19: chr6-24174967; COSMIC: COSV65829601; API