Genetic Variant DCDC1:c.5234-10_5234-6delTTTTT (chr11-30878716-TAAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387274.1(DCDC1):c.5234-10_5234-6delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,250,334 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DCDC1
NM_001387274.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

0 publications found

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]

DCDC1 links:

ENSG00000287373 (HGNC:):

ENSG00000287373 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387274.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCDC1	NM_001387274.1	MANE Select	c.5234-10_5234-6delTTTTT	splice_region intron	N/A	NP_001374203.1	A0A804HJA9
DCDC1	NM_001367979.1		c.5225-10_5225-6delTTTTT	splice_region intron	N/A	NP_001354908.1	M0R2J8-1
DCDC1	NM_020869.4		c.2546-10_2546-6delTTTTT	splice_region intron	N/A	NP_065920.2	B6ZDN3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCDC1	ENST00000684477.1	MANE Select	c.5234-10_5234-6delTTTTT	splice_region intron	N/A	ENSP00000507427.1	A0A804HJA9
DCDC1	ENST00000597505.5	TSL:5	c.5225-10_5225-6delTTTTT	splice_region intron	N/A	ENSP00000472625.1	M0R2J8-1
DCDC1	ENST00000406071.6	TSL:5	c.2546-10_2546-6delTTTTT	splice_region intron	N/A	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

140188

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000344

AC:

AN:

1250334

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

619822

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000379

AC:

AN:

26354

American (AMR)

AF:

0.000125

AC:

AN:

23916

Ashkenazi Jewish (ASJ)

AF:

0.000103

AC:

AN:

19470

East Asian (EAS)

AF:

0.0000296

AC:

AN:

33820

South Asian (SAS)

AF:

0.000107

AC:

AN:

65616

European-Finnish (FIN)

AF:

0.0000243

AC:

AN:

41162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4394

European-Non Finnish (NFE)

AF:

0.0000274

AC:

AN:

984244

Other (OTH)

AF:

0.0000195

AC:

AN:

51358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.242

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

140188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67788

African (AFR)

AF:

0.00

AC:

AN:

37310

American (AMR)

AF:

0.00

AC:

AN:

13966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4768

South Asian (SAS)

AF:

0.00

AC:

AN:

4378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65070

Other (OTH)

AF:

0.00

AC:

AN:

1898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-30878716-TAAAAAA-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over