11-30911356-C-T

Variant names:

• chr11-30911356-C-T
• rs144371995
• NM_001387274.1:c.3718G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001387274.1(DCDC1):​c.3718G>A​(p.Glu1240Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,605,604 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (32 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.971
• Publications: 5 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]

LOC105376611 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003991008).
• BP6: Variant 11-30911356-C-T is Benign according to our data. Variant chr11-30911356-C-T is described in ClinVar as Benign. ClinVar VariationId is 3351142.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 4 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.3718G>A	p.Glu1240Lys	missense	Exon 28 of 39	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.3718G>A	p.Glu1240Lys	missense	Exon 28 of 39	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.1039G>A	p.Glu347Lys	missense	Exon 9 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.3718G>A	p.Glu1240Lys	missense	Exon 28 of 39	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.3718G>A	p.Glu1240Lys	missense	Exon 26 of 36	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.1039G>A	p.Glu347Lys	missense	Exon 9 of 20	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152110 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00563

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00461 AC: 1086 AN: 235500 AF XY: 0.00452

Gnomad AFR exome AF: 0.000727

Gnomad AMR exome AF: 0.00195

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.00511

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00539 AC: 7831 AN: 1453376 Hom.: 32 Cov.: 31 AF XY: 0.00529 AC XY: 3820 AN XY: 721776

African (AFR) AF: 0.000749 AC: 25 AN: 33382

American (AMR) AF: 0.00197 AC: 86 AN: 43696

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.000476 AC: 40 AN: 83978

European-Finnish (FIN) AF: 0.0203 AC: 1075 AN: 53040

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.00574 AC: 6356 AN: 1107956

Other (OTH) AF: 0.00404 AC: 243 AN: 60150

GnomAD4 genome AF: 0.00472 AC: 718 AN: 152228 Hom.: 4 Cov.: 32 AF XY: 0.00516 AC XY: 384 AN XY: 74420

African (AFR) AF: 0.00111 AC: 46 AN: 41538

American (AMR) AF: 0.00510 AC: 78 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.0191 AC: 202 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00563 AC: 383 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00453 Hom.: 4

Bravo AF: 0.00354

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00364 AC: 442

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DCDC5-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.97
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.062	T
Vest4		0.36
MVP		0.43
ClinPred		0.013	T
GERP RS		4.2
gMVP		0.24
Mutation Taster		=297/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs144371995; hg19: chr11-30932903; COSMIC: COSV58003199; COSMIC: COSV58003199;