rs357968

Positions:

• chr2-3752906-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001287444.2(DCDC2C):​c.683+6C>T variant causes a splice donor 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. 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_donor_region, intron
• Scores: Splicing: ADA: 0.00008298
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DCDC2C	NM_001287444.2	c.683+6C>T		splice_donor_region_variant, intron_variant		ENST00000399143.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2C	ENST00000399143.9	c.683+6C>T		splice_donor_region_variant, intron_variant		5	NM_001287444.2	P1
DCDC2C	ENST00000537457.1	n.160-14848C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69261 AN: 151980 Hom.: 17996 Cov.: 33

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

GnomAD3 exomes AF: 0.569 AC: 83653 AN: 146900 Hom.: 24872 AF XY: 0.579 AC XY: 45758 AN XY: 79092

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 SAS exome AF: 0.707

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.: 43 AF XY: 0.540 AC XY: 372205 AN XY: 689084

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.567

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.456 AC: 69289 AN: 152098 Hom.: 18007 Cov.: 33 AF XY: 0.470 AC XY: 34925 AN XY: 74364

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.468

Alfa AF: 0.508 Hom.: 16316

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	12
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs357968; hg19: chr2-3800496;