dbSNP rs357968: DCDC2C:c.683+6C>T (chr2-3752906-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001287444.2(DCDC2C):c.683+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,549,262 control chromosomes in the GnomAD database, including 221,563 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 18007 hom., cov: 33)

Exomes 𝑓: 0.53 ( 203556 hom. )

Consequence

DCDC2C
NM_001287444.2 splice_region, intron

Scores

Splicing: ADA: 0.00008298

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.307

Publications

9 publications found

Variant links:

Genes affected

DCDC2C (HGNC:32696): (doublecortin domain containing 2C) Predicted to be involved in intracellular signal transduction. Located in cytoplasm and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

DCDC2C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2C	NM_001287444.2 link	c.683+6C>T		splice_region_variant, intron_variant	Intron 5 of 10	ENST00000399143.9	NP_001274373.1	A8MYV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2C	ENST00000399143.9 link	c.683+6C>T		splice_region_variant, intron_variant	Intron 5 of 10	5	NM_001287444.2	ENSP00000382097.4		A8MYV0
DCDC2C	ENST00000537457.1 link	n.160-14848C>T		intron_variant	Intron 2 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69261

AN:

151980

Hom.:

17996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.463

GnomAD2 exomes

AF:

0.569

AC:

83653

AN:

146900

AF XY:

0.579

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.579

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.680

Gnomad FIN exome

AF:

0.596

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.568

GnomAD4 exome

AF:

0.533

AC:

745383

AN:

1397164

Hom.:

203556

Cov.:

AF XY:

0.540

AC XY:

372205

AN XY:

689084

show subpopulations

African (AFR)

AF:

0.180

AC:

5683

AN:

31580

American (AMR)

AF:

0.578

AC:

20590

AN:

35634

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

14274

AN:

25168

East Asian (EAS)

AF:

0.719

AC:

25675

AN:

35724

South Asian (SAS)

AF:

0.700

AC:

55458

AN:

79180

European-Finnish (FIN)

AF:

0.586

AC:

28161

AN:

48050

Middle Eastern (MID)

AF:

0.560

AC:

3185

AN:

5686

European-Non Finnish (NFE)

AF:

0.521

AC:

561247

AN:

1078200

Other (OTH)

AF:

0.537

AC:

31110

AN:

57942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

16861

33722

50582

67443

84304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16250

32500

48750

65000

81250

<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

AF:

0.456

AC:

69289

AN:

152098

Hom.:

18007

Cov.:

AF XY:

0.470

AC XY:

34925

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.194

AC:

8038

AN:

41492

American (AMR)

AF:

0.540

AC:

8248

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

1981

AN:

3466

East Asian (EAS)

AF:

0.700

AC:

3625

AN:

5178

South Asian (SAS)

AF:

0.702

AC:

3390

AN:

4826

European-Finnish (FIN)

AF:

0.615

AC:

6500

AN:

10574

Middle Eastern (MID)

AF:

0.521

AC:

152

AN:

292

European-Non Finnish (NFE)

AF:

0.526

AC:

35775

AN:

67970

Other (OTH)

AF:

0.468

AC:

985

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1751

3502

5252

7003

8754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.506

Hom.:

17412

Bravo

AF:

0.438

Asia WGS

AF:

0.658

AC:

2286

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.024

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over