chr1-32212159-T-C

Position:

• chr1-32212159-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001099434.2(DCDC2B):​c.485T>C​(p.Leu162Pro) 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 pathogenic 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: 2.19

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2B	NM_001099434.2	c.485T>C	p.Leu162Pro	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.485T>C	p.Leu162Pro	missense_variant	4/9	1	NM_001099434.2	ENSP00000386870.1
DCDC2B	ENST00000487056.1	n.715T>C		non_coding_transcript_exon_variant	3/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249156 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

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

Feb 21, 2024

The c.485T>C (p.L162P) alteration is located in exon 4 (coding exon 4) of the DCDC2B gene. This alteration results from a T to C substitution at nucleotide position 485, causing the leucine (L) at amino acid position 162 to be replaced by a proline (P). 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	Pathogenic	0.56
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.62		Loss of stability (P = 0.0162);
MVP		0.93
MPC		0.40
ClinPred		0.96	D
GERP RS		3.3
Varity_R		0.76
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1400403103; hg19: chr1-32677760;