1-32212186-G-A

Position:

• chr1-32212186-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099434.2(DCDC2B):​c.512G>A​(p.Ser171Asn) 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: DCDC2B NM_001099434.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

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]

DCDC2B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37759477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2B	NM_001099434.2	c.512G>A	p.Ser171Asn	missense_variant	4/9	ENST00000409358.2	NP_001092904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2B	ENST00000409358.2	c.512G>A	p.Ser171Asn	missense_variant	4/9	1	NM_001099434.2	ENSP00000386870.1
DCDC2B	ENST00000487056.1	n.742G>A		non_coding_transcript_exon_variant	3/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.512G>A (p.S171N) alteration is located in exon 4 (coding exon 4) of the DCDC2B gene. This alteration results from a G to A substitution at nucleotide position 512, causing the serine (S) at amino acid position 171 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.028	D
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.29
Sift	Benign	0.043	D
Sift4G	Benign	0.068	T
Polyphen		0.60	P
Vest4		0.11
MutPred		0.67		Gain of catalytic residue at S171 (P = 0.0619);
MVP		0.81
MPC		0.052
ClinPred		0.23	T
GERP RS		2.6
Varity_R		0.076
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs753119607; hg19: chr1-32677787;