11-30931781-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001387274.1(DCDC1):c.2887C>T(p.Arg963Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,610,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034106016).
• BP6: Variant 11-30931781-G-A is Benign according to our data. Variant chr11-30931781-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3080416.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC1	NM_001387274.1	c.2887C>T	p.Arg963Trp	missense_variant	22/39	ENST00000684477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC1	ENST00000684477.1	c.2887C>T	p.Arg963Trp	missense_variant	22/39		NM_001387274.1	A2

Frequencies

GnomAD3 genomes AF: 0.000737 AC: 112 AN: 152012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000505 AC: 124 AN: 245526 Hom.: 0 AF XY: 0.000414 AC XY: 55 AN XY: 132938

Gnomad AFR exome AF: 0.000372

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.000985

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00103 AC: 1498 AN: 1457878 Hom.: 1 Cov.: 30 AF XY: 0.00102 AC XY: 743 AN XY: 725222

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000135

Gnomad4 ASJ exome AF: 0.000539

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.000499

GnomAD4 genome AF: 0.000736 AC: 112 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.000672 AC XY: 50 AN XY: 74358

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000695

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000470 AC: 57

EpiCase AF: 0.000716

EpiControl AF: 0.000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	0.17
Dann	Benign	0.86
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
Sift4G	Benign	0.12	T;T
Vest4		0.18
MVP		0.42
ClinPred		0.061	T
GERP RS		-1.7
gMVP		0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150997514; hg19: chr11-30953328; COSMIC: COSV60303529;