11-30905154-G-A

Variant names:

• chr11-30905154-G-A
• rs777624303
• NM_001387274.1:c.4115C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001387274.1(DCDC1):​c.4115C>T​(p.Ser1372Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000694 in 1,440,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11
• 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]

ENSG00000287373 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.745

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.4115C>T	p.Ser1372Leu	missense	Exon 31 of 39	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.4115C>T	p.Ser1372Leu	missense	Exon 31 of 39	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.1436C>T	p.Ser479Leu	missense	Exon 12 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.4115C>T	p.Ser1372Leu	missense	Exon 31 of 39	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.4115C>T	p.Ser1372Leu	missense	Exon 29 of 36	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.1436C>T	p.Ser479Leu	missense	Exon 12 of 20	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000470 AC: 1 AN: 212874 AF XY: 0.00000872

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000635

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000694 AC: 10 AN: 1440994 Hom.: 0 Cov.: 30 AF XY: 0.00000979 AC XY: 7 AN XY: 714946

African (AFR) AF: 0.0000303 AC: 1 AN: 33000

American (AMR) AF: 0.00 AC: 0 AN: 40960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39002

South Asian (SAS) AF: 0.00 AC: 0 AN: 84436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1099960

Other (OTH) AF: 0.00 AC: 0 AN: 59624

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000834 AC: 1

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	0.16
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.74	D
MetaSVM	Benign	-0.85	T
PhyloP100		5.1
PrimateAI	Benign	0.39	T
REVEL	Benign	0.27
Sift4G	Uncertain	0.0040	D
Vest4		0.82
MVP		0.63
ClinPred		0.94	D
GERP RS		4.4
gMVP		0.40
Mutation Taster		=94/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs777624303; hg19: chr11-30926701; COSMIC: COSV104602752; COSMIC: COSV104602752;