chr6-24357683-C-T

Variant names:

• chr6-24357683-C-T
• rs745333409
• NM_016356.5:c.68G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_016356.5(DCDC2):​c.68G>A​(p.Arg23His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCDC2 NM_016356.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

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]

KAAG1 (HGNC:21031): (kidney associated DCDC2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_016356.5
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016356.5. 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
	DCDC2	NM_016356.5	MANE Select	c.68G>A	p.Arg23His	missense	Exon 1 of 10	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.68G>A	p.Arg23His	missense	Exon 2 of 11	NP_001182539.1	Q9UHG0-1
	KAAG1	NR_174942.1		n.781C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.68G>A	p.Arg23His	missense	Exon 1 of 10	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000883243.1		c.68G>A	p.Arg23His	missense	Exon 2 of 11	ENSP00000553302.1
	KAAG1	ENST00000274766.2	TSL:6	n.781C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	0.0056	T
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.73	D
PhyloP100		6.1
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.31
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.25		Gain of sheet (P = 0.0049)
MVP		0.39
MPC		1.7
ClinPred		1.0	D
GERP RS		5.3
PromoterAI		0.0082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.063
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs745333409; hg19: chr6-24357911;