11-31065144-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001387274.1(DCDC1):c.2308C>G(p.Gln770Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000809 in 759,320 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (2 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011304498).
• BP6: Variant 11-31065144-G-C is Benign according to our data. Variant chr11-31065144-G-C is described in ClinVar as [Benign]. Clinvar id is 3051102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC1	NM_001387274.1	c.2308C>G	p.Gln770Glu	missense_variant	19/39	ENST00000684477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC1	ENST00000684477.1	c.2308C>G	p.Gln770Glu	missense_variant	19/39		NM_001387274.1	A2
DCDC1	ENST00000597505.5	c.2308C>G	p.Gln770Glu	missense_variant	17/36	5		A2
DCDC1	ENST00000437348.5	n.1016C>G		non_coding_transcript_exon_variant	9/12	5
DCDC1	ENST00000342355.8	c.*1383C>G		3_prime_UTR_variant, NMD_transcript_variant	19/22	2

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

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: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000605 AC: 137 AN: 226480 Hom.: 2 AF XY: 0.000436 AC XY: 54 AN XY: 123954

Gnomad AFR exome AF: 0.00757

Gnomad AMR exome AF: 0.000598

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: 0.0000187

Gnomad OTH exome AF: 0.000351

GnomAD4 exome AF: 0.000341 AC: 207 AN: 607114 Hom.: 2 Cov.: 0 AF XY: 0.000274 AC XY: 91 AN XY: 332170

Gnomad4 AFR exome AF: 0.00953

Gnomad4 AMR exome AF: 0.000386

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000115

Gnomad4 OTH exome AF: 0.000643

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00251 AC XY: 187 AN XY: 74426

Gnomad4 AFR AF: 0.00927

Gnomad4 AMR AF: 0.000851

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00289

ESP6500AA AF: 0.00584 AC: 22

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000663 AC: 79

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DCDC1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 13, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	11
Dann	Benign	0.93
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.011	T
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.080	T
Vest4		0.27
MVP		0.55
GERP RS		4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs189041969; hg19: chr11-31086691;