6-24174813-G-T

Position:

• chr6-24174813-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016356.5(DCDC2):​c.1348C>A​(p.Pro450Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: DCDC2 NM_016356.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

Genes affected

DCDC2 (HGNC:18141): (doublecortin domain containing 2) This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09708089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1348C>A	p.Pro450Thr	missense_variant	10/10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1348C>A	p.Pro450Thr	missense_variant	11/11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1348C>A	p.Pro450Thr	missense_variant	10/10	1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000378450.6	c.607C>A	p.Pro203Thr	missense_variant	3/3	1		ENSP00000367711.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	.;T
Eigen	Benign	0.079
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.025
Sift	Benign	0.24	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.97	D;B
Vest4		0.29
MutPred		0.24		.;Gain of phosphorylation at P450 (P = 0.0022);
MVP		0.81
MPC		0.13
ClinPred		0.32	T
GERP RS		4.8
Varity_R		0.079
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-24175041;