11-30906655-C-T

Variant names:

• chr11-30906655-C-T
• NM_001387274.1:c.3989G>A

Variant summary

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

The NM_001387274.1(DCDC1):​c.3989G>A​(p.Arg1330Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.972
• 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.3989G>A	p.Arg1330Lys	missense	Exon 30 of 39	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.3989G>A	p.Arg1330Lys	missense	Exon 30 of 39	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.1310G>A	p.Arg437Lys	missense	Exon 11 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.3989G>A	p.Arg1330Lys	missense	Exon 30 of 39	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.3989G>A	p.Arg1330Lys	missense	Exon 28 of 36	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.1310G>A	p.Arg437Lys	missense	Exon 11 of 20	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461436 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726978

⚠️ 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: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111726

Other (OTH) AF: 0.00 AC: 0 AN: 60364

⚠️ 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.88	T
PhyloP100		0.97
PrimateAI	Benign	0.31	T
REVEL	Benign	0.10
Sift4G	Uncertain	0.060	T
Vest4		0.50
MVP		0.68
ClinPred		0.89	D
GERP RS		4.9
gMVP		0.44
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

hg19: chr11-30928202;