1-32209299-C-T

Variant names:

• chr1-32209299-C-T
• rs903637223
• NM_001099434.2:c.206C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099434.2(DCDC2B):​c.206C>T​(p.Ala69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A69E) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DCDC2B NM_001099434.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3465314).

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.206C>T	p.Ala69Val	missense	Exon 1 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.206C>T	p.Ala69Val	missense	Exon 1 of 9	ENSP00000386870.1	A2VCK2
	DCDC2B	ENST00000906474.1		c.206C>T	p.Ala69Val	missense	Exon 1 of 9	ENSP00000576533.1
	DCDC2B	ENST00000487056.1	TSL:2	n.204C>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.96
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.34
Sift	Benign	0.15	T
Sift4G	Benign	0.12	T
Polyphen		0.59	P
Vest4		0.29
MutPred		0.55		Gain of ubiquitination at K72 (P = 0.0872)
MVP		0.92
MPC		0.33
ClinPred		0.95	D
GERP RS		4.1
PromoterAI		-0.012	Neutral
Varity_R		0.12
gMVP		0.23
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs903637223; hg19: chr1-32674900;