Variant 2-3778815-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_001287444.2(DCDC2C):c.955-1G>C variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.000000715 in 1,398,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

DCDC2C
NM_001287444.2 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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:

DCDC2C (HGNC:):

DCDC2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.062100455 fraction of the gene. Cryptic splice site detected, with MaxEntScore 10, offset of 2, new splice context is: ggtgtattttctccccacAGaca. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2C	NM_001287444.2 linkuse as main transcript	c.955-1G>C		splice_acceptor_variant, intron_variant		ENST00000399143.9	NP_001274373.1	A8MYV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2C	ENST00000399143.9 linkuse as main transcript	c.955-1G>C		splice_acceptor_variant, intron_variant		5	NM_001287444.2	ENSP00000382097.4		A8MYV0
DCDC2C	ENST00000537457.1 linkuse as main transcript	n.481-1G>C		splice_acceptor_variant, intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000663

AC:

AN:

150870

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398646

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cobalamin C disease

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Medicine Lab, University of California San Francisco

Oct 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.60

CADD

Pathogenic

DANN

Benign

0.90

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.65

GERP RS

4.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.85

SpliceAI score (max)

0.96

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.96

Position offset: 3

DS_AL_spliceai

0.95

Position offset: 1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over