1-32212149-G-T

Variant names:

• chr1-32212149-G-T
• NM_001099434.2:c.475G>T

Variant summary

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

The NM_001099434.2(DCDC2B):​c.475G>T​(p.Val159Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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: DCDC2B NM_001099434.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

DCDC2B (HGNC:32576): (doublecortin domain containing 2B) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. [provided by RefSeq, Sep 2010]

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_001099434.2. 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
	DCDC2B	NM_001099434.2	MANE Select	c.475G>T	p.Val159Leu	missense	Exon 4 of 9	NP_001092904.1	A2VCK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2B	ENST00000409358.2	TSL:1 MANE Select	c.475G>T	p.Val159Leu	missense	Exon 4 of 9	ENSP00000386870.1	A2VCK2
	DCDC2B	ENST00000906474.1		c.466G>T	p.Val156Leu	missense	Exon 4 of 9	ENSP00000576533.1
	DCDC2B	ENST00000487056.1	TSL:2	n.705G>T		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.16
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.011	D
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.21
MutPred		0.67		Loss of ubiquitination at K161 (P = 0.1473)
MVP		0.87
MPC		0.22
ClinPred		0.49	T
GERP RS		2.7
Varity_R		0.13
gMVP		0.32
Mutation Taster		=90/10	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

hg19: chr1-32677750;