11-30911356-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387274.1(DCDC1):​c.3718G>T​(p.Glu1240*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DCDC1 NM_001387274.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.971
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Glu1240*	stop_gained	Exon 28 of 39	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.3718G>T	p.Glu1240*	stop_gained	Exon 28 of 39	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.1039G>T	p.Glu347*	stop_gained	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>T	p.Glu1240*	stop_gained	Exon 28 of 39	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.3718G>T	p.Glu1240*	stop_gained	Exon 26 of 36	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.1039G>T	p.Glu347*	stop_gained	Exon 9 of 20	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453398 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721782

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.0000229 AC: 1 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 83978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107972

Other (OTH) AF: 0.00 AC: 0 AN: 60152

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.25	N
PhyloP100		0.97
Vest4		0.30
GERP RS		4.2
Mutation Taster		=100/100	disease causing (fs/PTC)

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;