11-30899605-C-G

Variant names:

• chr11-30899605-C-G
• rs75606205
• NM_001387274.1:c.4701G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001387274.1(DCDC1):​c.4701G>C​(p.Trp1567Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,574,150 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (5 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.27
• Publications: 1 publications found

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]

ENSG00000287373 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008265108).
• BP6: Variant 11-30899605-C-G is Benign according to our data. Variant chr11-30899605-C-G is described in ClinVar as Benign. ClinVar VariationId is 721756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387274.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC1	NM_001387274.1	MANE Select	c.4701G>C	p.Trp1567Cys	missense	Exon 34 of 39	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.4692G>C	p.Trp1564Cys	missense	Exon 34 of 39	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.2013G>C	p.Trp671Cys	missense	Exon 15 of 20	NP_065920.2	B6ZDN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC1	ENST00000684477.1	MANE Select	c.4701G>C	p.Trp1567Cys	missense	Exon 34 of 39	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.4692G>C	p.Trp1564Cys	missense	Exon 32 of 36	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.2013G>C	p.Trp671Cys	missense	Exon 15 of 20	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 638 AN: 151904 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.000937 AC: 200 AN: 213418 AF XY: 0.000662

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000829

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000642

Gnomad OTH exome AF: 0.000376

GnomAD4 exome AF: 0.000406 AC: 578 AN: 1422128 Hom.: 5 Cov.: 30 AF XY: 0.000363 AC XY: 256 AN XY: 705160

African (AFR) AF: 0.0139 AC: 449 AN: 32380

American (AMR) AF: 0.000843 AC: 34 AN: 40336

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25234

East Asian (EAS) AF: 0.00 AC: 0 AN: 38776

South Asian (SAS) AF: 0.0000510 AC: 4 AN: 78416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51574

Middle Eastern (MID) AF: 0.00177 AC: 10 AN: 5644

European-Non Finnish (NFE) AF: 0.0000202 AC: 22 AN: 1091168

Other (OTH) AF: 0.000990 AC: 58 AN: 58600

GnomAD4 genome AF: 0.00419 AC: 637 AN: 152022 Hom.: 7 Cov.: 32 AF XY: 0.00378 AC XY: 281 AN XY: 74322

African (AFR) AF: 0.0140 AC: 582 AN: 41488

American (AMR) AF: 0.00262 AC: 40 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67914

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.000699 Hom.: 0

Bravo AF: 0.00505

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00106 AC: 128

Asia WGS AF: 0.000869 AC: 3 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DCDC5-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.87	T
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
REVEL	Benign	0.24
Sift4G	Uncertain	0.0020	D
Vest4		0.67
MVP		0.53
ClinPred		0.018	T
GERP RS		4.7
gMVP		0.10
Mutation Taster		=96/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs75606205; hg19: chr11-30921152;